Cheng YJ, Gregg EW, Geiss LS, Imperatore G, Meeication DE, Zhang Diabetes prevention through medication, et al. Medicatikn incidence of CVD mortality was Economic evaluation of therapeutic interventions to prevent type 2 diabetes in Canada. The Lancet. The development of insulin resistance, in which the action of insulin on glucose metabolism is blunted, occurs early in the pathogenesis of dysglycaemia.

Diabetes prevention through medication -

Lifestyle choices, including eating a healthy diet, exercising and staying at a healthy weight, are key to managing type 2 diabetes. But you also might need to take medication to keep your blood sugar, also called glucose, at a healthy level. Sometimes one medication is enough. In other cases, taking several medications works better.

The list of medications for type 2 diabetes is long and can be confusing. Take time to learn about these medicines — how they're taken, what they do and what side effects they may cause.

That can help you get ready to talk to your health care provider about diabetes treatment choices that are right for you. Several classes of type 2 diabetes medicines exist. Each class of medicine works in a different way to lower blood sugar. A medication may work by:.

Each class of medicine has one or more medications. Some of these medications are taken by mouth, while others must be taken as a shot. Below is a list of common diabetes medications. Other medications are available too. Ask your health care provider about your choices and the pros and cons of each.

People with liver problems or a history of heart failure shouldn't take this kind of diabetes medicine. No one diabetes treatment is best for everyone. What works for one person may not work for another. Your health care provider can explain how one medication or multiple medications may fit into your diabetes treatment plan.

Sometimes combining medicines may increase the effectiveness of each individual medicine to lower blood sugar. Talk to your provider about the pros and cons of specific diabetes medications for you.

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Check out these best-sellers and special offers on books and newsletters from Mayo Clinic Press. Aroda, … John B. Matthias Blüher, Julio Rosenstock, … Anita M. Davies, David A. A high prevalence of prediabetes is fuelling the evolving global diabetes pandemic, and optimisation of management of prediabetes is an urgent global clinical priority.

A broad evidence base from clinical trials and previous clinical experience support the efficacy and safety profiles of metformin for diabetes prevention, and highlight subjects in which metformin will be most effective. Current evidence supports a role for metformin in diabetes prevention, given in addition to lifestyle intervention, in people with prediabetes.

It is well accepted that type 2 diabetes is strongly linked with high morbidity and mortality rates [ 1 ]. The markedly increased prevalence of diabetes in recent decades places a severe burden on healthcare systems worldwide [ 2 , 3 ].

The diagnosis of diabetes is made according to the level of glycated haemoglobin HbA1c or plasma glucose. The purpose of this review was to summarise the evidence base for the use of metformin in patients with prediabetes. The defects in glucose metabolism that underlie type 2 diabetes begin many years before the diagnosis of diabetes is made [ 6 , 7 ].

The development of insulin resistance, in which the action of insulin on glucose metabolism is blunted, occurs early in the pathogenesis of dysglycaemia. Increased secretion of insulin initially compensates for the presence of insulin resistance; however, a simultaneous and progressive loss of β-cell mass and β-cell function limits the ability of the pancreas to maintain euglycaemia by increasing insulin secretion [ 8 ].

The early manifestations of prediabetic dysglycaemia represent one or both of [ 9 ]:. impaired glucose tolerance IGT , in which postprandial glucose control is impaired but fasting plasma glucose FPG is normal;. impaired fasting glucose IFG , in which a chronic elevation of FPG occurs in the absence of a deterioration in postprandial glucose control.

Table 1 shows the usually accepted diagnostic criteria for the diagnosis of prediabetes based on measurements of glycaemia [ 4 , 8 — 10 ]. A simple blood test is sufficient to diagnose IFG, while a 75 g oral glucose tolerance test OGTT is required for the diagnosis of IGT.

Diagnostic criteria from the American Diabetes Association also support a diagnosis of prediabetes but not a specific diagnosis of IFG or IGT in subjects with elevated, but non-diabetic, levels of HbA 1c 5. A study from the US National Health and Nutrition Examination Survey NHANES , published in , found that the use of fasting glucose identified twice as many subjects as having prediabetes compared with the use of HbA1c 28 vs.

Moreover, HbA1c does not correlate accurately with glucose levels in individuals and may therefore over- or underestimate the current level of glycaemic control [ 14 ].

Accordingly, while HbA1c is a convenient measurement for evaluating long-term glycaemic control in diabetes, the impact of its use as a diagnostic criterion for prediabetes will require further study.

The loss of glycaemic control as insulin resistance and β-cell dysfunction develops is insidious, progressive and continuous [ 6 , 7 ]. The prevalence of both type 2 diabetes and prediabetes has increased rapidly in recent years. Similar data are available from the Augsburg Germany cohort of the large, international Monitoring Trends and Determinants on Cardiovascular Diseases MONICA study, conducted in subjects aged 25—74 years.

Prevalence of prediabetes in three cohorts without a prior diagnosis of diabetes in the US, i. Screening for Impaired Glucose Tolerance SIGT , the Third National Health and Nutrition Examination Survey NHANES III , and the National Health and Nutrition Examination Survey — NHANES — Adapted from data presented by Rhee et al.

IFG impaired fasting glucose, IGT impaired glucose tolerance. People diagnosed with combined IFG and IGT are at increased risk of developing diabetes compared with individuals with only one of these conditions.

Even modest, long-term elevations of plasma glucose, consistent with those associated with IGT or IFG have been associated with damage to the vasculature [ 21 — 26 ].

Retinopathy was diagnosed in 7. Prediabetic dysglycaemia also increases the risk of adverse cardiovascular events such as myocardial infarction, stroke or cardiovascular death; see reviews elsewhere [ 28 , 29 ].

In addition, as an insulin resistant state, prediabetes frequently coexists with other cardiovascular risk factors associated with the metabolic syndrome, such as elevated blood pressure and dyslipidaemia [ 30 ].

Insulin resistance, which appears early in the pathogenesis of dysglycaemia and is likely to be present in most prediabetic subjects, is itself a powerful prognostic indicator for an increased risk of diabetes or cardiovascular disease [ 6 — 8 ].

Intervention in prediabetes is known to prevent or delay the onset of diabetes, a state known to be associated with markedly elevated cardiovascular risk [ 31 ]. The appearance in the circulation of the cardiac-specific isozyme of troponin is indicative of damage to the myocardium, and is associated with an adverse long-term prognosis [ 32 ].

Accordingly, the presence of prediabetes may be associated with subclinical damage to the myocardium. It is clear that the increased risk of adverse cardiovascular outcomes associated with type 2 diabetes does not begin at the diagnostic cutoff for plasma glucose or HbA1c at which the condition is diagnosed.

Rather, there appears to be a continuum of increased microvascular and macrovasular risk that extends to levels of glycaemia well below these cutoffs.

While it seems reasonable to hypothesise that correction of prediabetic dysglycaemia might also reduce the future risk of adverse cardiovascular outcomes, further evidence from clinical trials is needed to demonstrate improved long-term outcomes in this setting [ 31 ].

Prediabetes IGT and IFG and clinically established type 2 diabetes are each characterised by insulin resistance and β-cell dysfunction, and represent a continuum of increasing severity of dysglycaemia, as described above.

Accordingly, the overall principles of managing diabetes and prediabetes are similar [ 4 ]. People at risk of diabetes, particularly those who are overweight or obese, or women with a history of gestational diabetes, should be tested for the presence of prediabetes or diabetes alongside other cardiovascular risk factors.

Lifestyle intervention remains the cornerstone of care for individuals with prediabetes or diabetes, based on an improved diet and regular moderate physical exercise with the aim of achieving weight loss in overweight or obese subjects Table 2 [ 4 , 34 ].

Pharmacologic therapy with interventions used to promote weight loss e. orlistat or bariatric surgery or with drugs usually used for the management of type 2 diabetes metformin, thiazolidinediones, α-glucosidase inhibitors or basal insulin have also been shown to effectively delay or prevent the conversion of prediabetes to diabetes described below.

Currently, metformin is the only pharmacologic agent recommended for the prevention or delay of type 2 diabetes in at-risk subjects due to its effectiveness as demonstrated in well-designed trials see below , its generally good tolerability aside from the well-understood gastrointestinal side effects associated with this agent and its low cost [ 4 , 34 ].

At present, metformin has no formal indication for this purpose in most countries Turkey, Poland, and The Philippines are exceptions , although such an indication may become established in many countries in the future. The remainder of this review will focus in detail on the therapeutic profile of metformin for the management of prediabetes and other insulin-resistant states that predispose to the subsequent development of type 2 diabetes.

A brief summary of the pharmacologic mechanism and clinical actions of metformin is provided in this review as these are relevant to its therapeutic effects on prediabetic subjects. Metformin acts primarily by enhancing the action of insulin in the liver to reduce the rate of hepatic glucose production [ 35 ].

Improvements in insulin action in skeletal muscle also contribute to the therapeutic actions of metformin, mainly resulting in increased non-oxidative glucose disposal [ 36 ]. Together, these actions reduce blood glucose in the setting of hyperglycaemia, with very little potential for inducing hypoglycaemia [ 37 ].

An increase in anaerobic metabolism in the intestinal wall is also probably a clinically significant antihyperglycaemic mechanism of metformin [ 38 , 39 ]. Metformin may also induce upregulation of the expression of GLP-1 receptors on the surface of pancreatic β-cells [ 41 ]. As GLP-1 enhances glucose-dependent insulin release from the pancreas, this mechanism may provide modest support to the function of the β cell [ 40 , 43 ].

An effect of metformin on the gut microbiome has also been postulated [ 44 ]. Mechanistically, metformin appears to inhibit mitochondrial respiration at the level of respiratory chain complex I [ 45 ]. The resulting shift in cellular energy balance increases the activity of AMP kinase, which promotes the action of insulin and reduces hepatic gluconeogenesis [ 45 ].

An increase in circulating cyclic adenosine monophosphate cAMP also opposes the hyperglycaemic action of glucagon [ 45 , 46 ]. Other studies have shown that metformin enhances the action of DPP4 inhibitors by either reducing the activity of DPP4 or enhancing secretion of GLP-1 [ 47 , 48 ].

Metformin relies on transport into cells via the organic cation transporter-1 OCT1 for its clinical action, and polymorphisms of this transporter influence the efficacy of metformin in type 2 diabetes [ 49 , 50 ]. The relevance of this mechanism for diabetes prevention has yet to be determined and further research is required.

In the UK Prospective Diabetes Study UKPDS , metformin was the first antidiabetic drug shown to improve cardiovascular prognosis [ 51 ]; clinically significant reductions in the risk of a range of adverse outcomes were observed, relative to the standard diet-based treatment of the time, including all-cause mortality, diabetes-related death and myocardial infarction, which were greater than those expected from improved blood glucose control per se.

A second trial in insulin-treated patients also demonstrated improved cardiovascular outcomes in patients randomised to metformin relative to placebo [ 53 ]. Improved cardiovascular outcomes with metformin is included in the European labelling of this drug.

The forthcoming Glucose Lowering In Non-diabetic hyperglycaemia Trial GLINT trial is expected to definitively demonstrate the extent to which metformin protects the vasculature in a prediabetic population at high risk of adverse cardiovascular events [ 54 ].

Improvements in glycaemia during treatment with metformin were insufficient to explain the improved cardiovascular outcomes observed in the UKPDS [ 52 ].

A recent uncontrolled study in insulin-treated type 2 diabetes patients showed that long-term treatment with metformin average 4. Numerous other mechanisms have been proposed to explain the protective effect of metformin on the vasculature in the UKPDS, including improved haemostasis reduced potential for atherothrombotic disease , reduced vascular inflammation, amelioration of oxidative stress, inhibition of the formation of advanced glycation end-products, improved function of the microcirculation and modification of the cellular processes that occur during atherogenesis [ 56 ].

The principal side effects of metformin occur in the gastrointestinal tract mostly diarrhoea ; these can be minimised by starting metformin at a low dose and increasing the dose cautiously and infrequently cause treatment discontinuation [ 57 ].

Prolonged-release formulations of metformin are available, which appear to improve gastrointestinal tolerability compared with the immediate-release formulation [ 58 ]. Biguanide antidiabetic agents have long been associated with an increased risk of lactic acidosis but it is now clear that the risk of lactic acidosis with metformin is extremely low when this agent is prescribed correctly [ 59 , 60 ].

Contraindications to metformin intended to reduce the risk of lactic acidosis, as described in its labelling, generally reflect cardiovascular morbidity and renal dysfunction that might provoke accumulation of metformin in the body—these conditions are less likely to be prevalent in a prediabetic population compared with a population with established type 2 diabetes at higher risk of long-term complications of the disease.

Treatment with metformin has also been associated with clinically significant vitamin B 12 deficiency in some patients, where neuropathy arising from low levels of B 12 may mimic diabetic neuropathy [ 61 ]. A meta-analysis of 29 studies that included a total of patients found that metformin increased the risk of B 12 deficiency, with an odds ratio OR of 2.

Monitoring B 12 levels, with supplementation where necessary, may be useful in all subjects receiving long-term treatment with metformin. The principal features and main results of major trials that evaluated metformin for diabetes prevention are shown in Table 3 [ 19 , 64 — 69 ].

Significant reductions in the risk of progressing from prediabetes principally IGT to type 2 diabetes in subjects treated with metformin were observed in populations in:. The US, in the DPP [ 19 ]. India, in the Indian DPP IDDP [ 65 ].

China [ 66 , 68 ]. Canada, in the CAnadian Normoglycemia Outcomes Evaluation CANOE [ 64 ]. Pakistan [ 67 ]. These trials will be described in greater detail in the following sections. Details of trials that did not evaluate metformin are also shown in Table 3 , for comparison [ 70 — 78 ].

Lifestyle intervention was consistently effective in reducing the risk of diabetes and should be recommended for all subjects at risk of diabetes or cardiovascular disease, irrespective of other therapies prescribed.

It is also clear that thiazolidinediones, α-glucosidase inhibitors and weight-reducing interventions also have the potential to prevent or delay the onset of diabetes in prediabetic subjects.

A post hoc analysis of the STOP-NIDDM Study to Prevent Non-Insulin-Dependent Diabetes Mellitus trial [ 72 ] suggested a reduced incidence of hypertension and cardiovascular disease for acarbose versus placebo in subjects with IGT, although the number of events was low [ 73 ].

The effects of metformin on diabetes outcomes in the DPP, and also on cardiometabolic endpoints relevant to diabetes prevention, are discussed in detail here. Health economic analyses are discussed separately in a later section, alongside comparable analyses from other trials.

A total of subjects were randomly assigned to a multifactorial intensive lifestyle intervention, metformin plus standard lifestyle advice or placebo plus standard lifestyle advice in the DPP [ 19 ].

It is unfortunate that metformin plus intensive lifestyle intervention was not studied in the DPP as this combination might be expected to provide additive protection from conversion to type 2 diabetes in a prediabetic population although no such additive benefits were observed in the IDDP; see below.

Participants in the DPP were followed up for long-term clinical outcomes in the DPP Outcomes Study DPPOS , which is described separately below [ 69 ]. Inclusion criteria relating to FPG 5. Standard lifestyle advice consisted of an annual meeting with a healthcare professional, and written material on a healthy lifestyle.

The intensive lifestyle group received face-to-face instruction and advice on maintaining a healthy lifestyle individually and in groups. The study was terminated after 2. Reductions in body weight were maximal in the intensive lifestyle intervention and metformin groups at 0. Mean weight loss at 4 years was 5.

Increased physical activity was only seen in the intensive lifestyle intervention group. New-onset diabetes occurred at a rate of The number needed to treat to prevent one case of incident diabetes was 6.

The efficacy of metformin approached that of the intensive lifestyle intervention in younger subjects and those with higher BMI or FPG at baseline Fig. The median delay in diabetes onset was estimated at 11 years for the intensive lifestyle intervention and 3 years for metformin [ 81 ].

Mean changes in weight during the randomised phase of the Diabetes Prevention Program. Placebo and metformin were administered in combination with standard lifestyle advice.

Adapted from data presented by the Diabetes Prevention Program Research Group [ 19 ]. Effects of treatments in the Diabetes Prevention Program on the risk of diabetes following stratification of the population for age, FPG or BMI at baseline. a Age at baseline; b BMI at baseline; c FPG at baseline.

Comparisons shown are for ILI vs. P, M vs. P, and ILI vs. In each case, a more strongly negative change in risk signifies greater efficacy of the first named agent. FPG fasting plasma glucose, BMI body mass index, ILI intensive lifestyle intervention, M metformin, P placebo. Lower fasting glucose, weight loss, younger age and higher insulin secretion predicted reversion from IGT to normal glucose tolerance in the DPP [ 82 ].

There was a non-significant trend for reversion to normal glucose tolerance in the metformin group, which was significant for subjects with both IGT and IFG at baseline. A total of subjects randomised to placebo or metformin and without diabetes at study end participated in a washout study, involving an evaluation of glycaemic status after 1—2 weeks off treatment [ 83 ].

A lower risk of diabetes on metformin OR 0. Taking the combined rate of conversions to diabetes from the double-blind and washout phases showed that some of the effect of metformin on the risk of diabetes had persisted OR 0.

Neither age nor BMI at baseline influenced these findings. Treatment with placebo was discontinued while treatment with metformin mg twice daily was continued unless changes to medication were required for managing diabetes or for other reasons. All subjects received instruction on following a healthy lifestyle based on aspects of the intensive lifestyle intervention.

The study population are being followed-up as an observational cohort for composite microvascular and macrovascular endpoints in addition to incident diabetes [ 84 ]. Ten-year effects on diabetes incidence and weight loss were evaluated in subjects from the original intensive lifestyle intervention group, from the original metformin group, and from the original placebo group.

Mean body weight at the end of the randomised phase of the DPP was During the DPPOS, the original intensive lifestyle intervention group regained approximately 1 kg, while weight loss in the original metformin and placebo groups was similar for the beginning and end of the observational phase in the DPPOS.

Thus, mean weight was similar for patients originally randomised to the intensive lifestyle intervention or metformin after 10 years of randomised and observational follow-up.

Diabetes incidence rates per person-years during the DPPOS, according to treatment assignment in the DPP, were 4. The apparent benefit for metformin relative to lifestyle intervention during the DPPOS phase was due to reduced diabetes incidence rates in the metformin and placebo group compared with an increasing rate in the intensive lifestyle group.

patients with genetic susceptibility to diabetes in the metformin and placebo groups had already developed diabetes by the time the DPPOS commenced, was likely due to the reduced diabetes incidence in the other groups [ 85 ].

Surprisingly, it appeared that the provision of a lifestyle intervention for the metformin and placebo groups was not associated with the declining diabetes incidence in these groups.

The risk of developing diabetes was lowest for patients who had reverted from IGT to normal glucose regulation, irrespective of original treatment assignment [ 86 ]. Increased β-cell function and insulin resistance were significantly associated with reversion to normal glucose tolerance and inversely associated with the risk of developing diabetes.

An association between the use of antidepressants and increased risk of diabetes see below persisted into the DPPOS phase [ 87 ]. Improvements in lipid parameters low-density lipoprotein [LDL]-cholesterol, triglycerides and high-density lipoprotein [HDL]-cholesterol and blood pressure occurred similarly between the original treatment groups during the year follow-up period; however, there was a lower rate of use of pharmacologic lipid-modifying and antihypertensive therapy in the original intensive lifestyle intervention group, relative to other groups [ 88 ].

During the DPP, gastrointestinal side effects were more common on metformin relative to placebo average of 28 vs. The rate of these adverse events declined over time in the original metformin group so that the incidence was similar to that observed in the original placebo group by the end of the DPPOS [ 89 ].

No unexpected adverse events were encountered. There were three cases of anaemia presenting as serious adverse events two on metformin, one on placebo and no cases of lactic acidosis or hypoglycaemia presenting as a serious AE during nearly 18, subject-years of follow-up.

Numerous other analyses from the DPP have been presented, with regard to the effects of interventions on the risk of developing type 2 diabetes. The main outcomes from a series of selected analyses are summarised below. Changes in body weight, insulin sensitivity, and insulin secretion independently predicted the risk of developing diabetes in the DPP irrespective of treatment allocation [ 91 ].

The reduced diabetes risk on intensive lifestyle intervention in the DPP was strongly associated with loss of visceral fat, but the effect of metformin was independent of changes in adiposity [ 92 — 94 ].

African American women lost less weight compared with other ethnicities in the intensive lifestyle intervention group of the DPP, although there was no difference between ethnicities for weight loss in the metformin group [ 95 ].

Gender did not strongly predict changes in diabetes risk during weight loss overall [ 96 ]. Adherence to metformin therapy was higher for older versus younger patients [ 97 ]. Adherence decreased in line with increasing numbers of potential barriers to adherence, and increased in line with the number of overlapping strategies used by patients to maintain good adherence.

Intensive lifestyle was more effective than metformin for women without prior GDM 49 vs. Health-related quality of life HRQoL improved modestly in the intensive lifestyle intervention arm of the DPP, mainly associated with weight loss, with no significant change in other treatment arms [ 99 ].

However, some HRQoL measures were reduced further in patients who became diabetic while undertaking intensive lifestyle intervention relative to those who became diabetic while taking metformin [ ].

It may be important to manage expectations of patients undertaking intensive lifestyle interventions, who may benefit from a delay in diabetes onset but remain at high long-term risk of diabetes.

Circulating adiponectin levels increased significantly on intensive lifestyle intervention but not on metformin or placebo; changes in this parameter were associated with significantly lower diabetes risk only in the intensive lifestyle intervention group [ ]. The relationship between adiponectin and diabetes risk in the intensive lifestyle intervention group was attenuated by adjustment for weight but remained significant.

The severity of depression was similar among the randomised treatment groups in the DPP [ ]. Continuous use of antidepressants predicted a higher risk of diabetes in the intensive lifestyle intervention and placebo groups but not in the metformin group [ 97 , ].

Greater alcohol consumption was associated with lower insulin secretion and a lower adjusted risk of diabetes for intensive lifestyle intervention and metformin but not for placebo [ ]. Improvements in triglycerides occurred in all groups but were larger with intensive lifestyle intervention.

Intensive lifestyle intervention increased mean HDL-cholesterol and decreased the incidence of the atherogenic LDL phenotype B.

Total and LDL-cholesterol were similar between groups. Fewer subjects on intensive lifestyle intervention required pharmacologic treatment for cardiovascular risk factors versus placebo or metformin at 3 years. Alterations in cardiovascular risk factors tended to parallel changes in glycaemic status, with little difference between treatment groups in cardiovascular risk factor status for subjects who progressed to type 2 diabetes [ ].

Cardiovascular risk factor status was generally most favourable for the intensive lifestyle intervention arm. Changes in urinary albumin:creatinine ratio varied little between treatments and exerted little effect on the risk of diabetes [ , ].

Modest, but significant, improvements in serum alanine aminotransferase a marker of hepatic function and C-reactive protein a marker of systemic inflammation were mediated by weight loss [ , ].

A high genetic risk score GRS based on deleterious alleles at 32 lipid-associated single-nucleotide polymorphisms SNPs predicted adverse lipid changes only in the intensive lifestyle intervention arm of the DPP [ ].

Higher values of a GRS based on 34 loci associated with type 2 diabetes predicted an increased risk of developing type 2 diabetes in the DPP overall but without influence on the effect of individual treatments [ ]. Key studies of individual mutations that influenced the risk of diabetes in the DPP are summarised in Table 4.

Notably, the response to metformin in the DPP was associated, with varying extents, with variations in the genes for transporters of metformin and components of AMP kinase, with individual mutations increasing or decreasing the risk of diabetes [ ].

Of 16 SNPs known to be associated with obesity, only one was significantly associated with metformin for long-term weight loss NEGR1 rs ; other SNPs were usually associated with short- or long-term weight loss with intensive lifestyle intervention, or irrespective of treatment [ ]. Protective effects of polymorphisms in the WFS1 gene that are associated with improved β-cell function may be amplified by intensive lifestyle intervention [ ].

Subjects with the diabetes risk-conferring TT genotype at rs in the TCF7L2 gene associated with diminished β-cell function were more likely to progress to diabetes than subjects with the AA genotype at this location [ ]; however, the interaction between genotype and treatment allocation did not achieve statistical significance.

No effect on diabetes risk was observed for genetic variants previously reported to be associated with disturbed glucose regulation fasting glucose, impaired β-cell function or insulinogenic index [ ], or for the C allele at the rs polymorphism in the ataxia-telangiectasia-mutated gene, which has been previously associated with a larger clinical response to metformin [ ].

The IDDP differed from the DPP in that an intensive lifestyle intervention and metformin were evaluated separately and in combination, each in comparison with a control group given standard healthcare advice [ 65 ].

Metformin was initially given at a dose of mg, titrated to mg twice daily after 2 weeks, according to tolerability. The dose was lower than that used in the DPP to account for the smaller average body size of South Asian versus American subjects.

Similar reductions in the risk of diabetes were observed in active treatment groups, with no sign of synergy between the lifestyle intervention and metformin Table 3.

Numbers needed to treat ranged between 6. There were no significant changes in body weight at 3 years in any group. The proportions of patients with elevated LDL-cholesterol decreased in all active treatment groups but not in the control group, while the prevalence of hypertension increased significantly in all groups, irrespective of treatment [ ].

As in the DPP, subjects with more severe insulin resistance or β-cell dysfunction at baseline were more likely to develop diabetes, and diabetes prevention was associated with improvements in these parameters [ ]. However, although insulin resistance HOMA-IR increased in line with the number of criteria for the metabolic syndrome, the presence or absence of metabolic syndrome criteria per se did not influence the risk of developing diabetes HR 1.

The low-dose combination therapy with rosiglitazone and metformin to prevent type 2 diabetes mellitus study CANOE sought to avoid the common adverse events associated with rosiglitazone oedema with increased risk of incident heart failure and metformin gastrointestinal side effects, principally diarrhoea by using rosiglitazone and metformin in a low-dose combination in a 4-year, randomised, placebo-controlled study in subjects with IGT [ 64 ].

The reduction in the risk of new-onset type 2 diabetes in the CANOE study was at least comparable to the risk reductions observed in the other studies using metformin, and was also comparable to the risk reductions observed with intensive lifestyle interventions or rosiglitazone in other studies Table 3.

However, the combination treatment did not alter the rate of progression of decreases in insulin sensitivity and β-cell function [ ].

Current prescribing restrictions relating to safety concerns with thiazolidinediones [ ] potentially limit any future role for thiazolidinedione-based combinations in diabetes prevention. However, the CANOE study established an important principle in that effective diabetes prevention can be achieved using low-dose combinations of drugs that minimise the potential for side effects.

Metformin significantly prevented diabetes when analysed in either of these ways, and also when only considering placebo-controlled data or the use of low doses of metformin in Asian subjects Fig.

A further systematic review, which did not attempt a meta-analysis, concluded that while there is substantial evidence that lifestyle or pharmacologic interventions effectively delay or prevent diabetes, there was insufficient evidence to compare their effectiveness [ ].

Main results of a meta-analysis of diabetes prevention studies with metformin. Adapted from data presented by Lily and Godwin [ ].

ITT intention-to-treat analysis. Larger effects were observed in subjects with prediabetic dysglycaemia absolute risk difference The reduction in diabetes incidence was associated with reduced FPG, total cholesterol and LDL-cholesterol, and increased HDL-cholesterol. Further studies, described below, did not include new-onset diabetes in their endpoints but evaluated the effect of metformin on parameters relevant to diabetes prevention primarily insulin resistance in non-diabetic populations.

The IDDP [ 53 ] and the studies by Wenying et al. A study in 32 subjects with IGT showed that exercise training, metformin, and exercise training with metformin all increased insulin sensitivity relative to a placebo control, with no significant difference between active treatment groups [ ].

A post hoc analysis of the 1-year, randomised Biguanides and the Prevention of the Risk of Obesity BIGPRO1 study demonstrated significant improvements for metformin vs. placebo in FPG, systolic BP, and total and LDL-cholesterol in abdominally obese subjects with IGT or IFG [ ].

Similar benefits of metformin were observed in subjects who met the inclusion criteria for the DPP in this analysis. Randomisation of 40 participants in the Botnia cohort in Sweden, who had IGT and a first-degree relative with type 2 diabetes, resulted in improved glucose homeostasis that was sustained over 12 months [ ].

In addition, little information is available on optimal dietary management for use alongside metformin: the RESIST Researching Effective Strategies to Improve Insulin Sensitivity in Children and Teenagers study is currently comparing two diets in obese, metformin-treated children and adolescents with IFG, IGT or elevated insulin resistance [ ].

Again, the studies described here did not include new-onset diabetes as an endpoint, and effects on clinical parameters relevant to diabetes prevention are described here. Table 5 summarises details of clinical evaluations of metformin in paediatric patients without diabetes at baseline [ — ].

Metformin was associated with significant reductions versus placebo in mean weight treatment difference —4. Significant improvements also occurred in the metformin group in subcutaneous abdominal fat measured using CT scanning. Metformin markedly reduced body weight by 6.

The Metformin in Obese Children and Adolescents trial in the UK randomised obese children or adolescents to metformin or placebo for 6 months [ ].

Another randomised, placebo-controlled study in 52 glucose-intolerant paediatric subjects showed that 12 weeks of treatment with metformin mg twice daily significantly reduced levels of resistin a hormone associated with insulin resistance , HOMA-IR and HbA1c [ ].

A number of randomised, controlled trials have demonstrated benefits in terms of improved glycaemic regulation and weight loss associated with coadministration of metformin with antipsychotic gents [ — ].

Meta-analyses found a weight benefit for metformin versus placebo of 5 kg [ ], 3. One meta-analysis found a non-significant reduction in the risk of type 2 diabetes relative risk 0.

Three studies showed no benefit for metformin on body weight in this setting [ — ]. The use of metformin for diabetes prevention was cost effective in analyses based on the DPP, whether based on a within-trial analysis, from a societal perspective, or on Markov modelling studies that extrapolated the DPP findings to the health systems of other countries Table 6 [ 81 , — ].

A year economic evaluation of interventions in the DPP and DPPOS showed that metformin was cost saving relative to placebo, with comparable quality-adjusted life-years QALY gained, while intensive lifestyle intervention resulted in a higher average number of QALY gained [ ].

Incremental cost-effectiveness ratios were generally substantially higher from a societal perspective. Table 7 summarises health economic analyses from this and other studies [ , — ]. Metformin or intensive lifestyle intervention were also cost-effective strategies for prevention of diabetes in at-risk subjects identified opportunistically or by screening in Germany [ ], the US [ , ], Canada [ ] or Australia although metformin plus intensive lifestyle intervention was not cost effective here [ ].

Intensive lifestyle interventions were usually more cost effective than metformin due to the greater reductions in diabetes incidence with intensive lifestyle intervention versus metformin in the DPP, and hence greater projected reductions in the incidence of complications of diabetes in studies with long time horizons.

Several studies demonstrated that screening for prediabetes was cost effective, compared with no screening, when subjects identified as prediabetic would be treated subsequently with a lifestyle intervention or metformin. A number of guidelines have been written on the management of subjects with prediabetes Table 8 [ 4 , 10 , 34 , — ].

Most place their primary focus on lifestyle intervention. Where pharmacologic therapy is considered as a second-line intervention, most guidelines, including major international guidelines from expert groups in the US, Europe, and the International Diabetes Federation favour the use of metformin.

The recent Position Statement from the American Diabetes Association recommends that metformin has the strongest evidence base of pharmacological agents for diabetes prevention [ 4 ].

Such a recommendation is consistent with a study demonstrating that most prediabetic subjects in the US would meet American Diabetes Association criteria for consideration for treatment with metformin Fig. It should be noted that these recommendations are made despite the lack of an indication for diabetes prevention with metformin in most countries, including the US and most of Europe.

Proportions of prediabetic subjects in the US meeting ADA criteria for treatment with metformin. Columns show estimated proportions meeting ADA criteria for use of metformin for IGT or IFG, pooled from data presented for three cohorts. ADA American Diabetes Association, IGT impaired glucose tolerance, IFG impaired fasting glucose.

The evolving global diabetes pandemic heralds a future increase in the burden of complications of diabetes on patients, families and national healthcare systems. As most individuals with prediabetes will eventually go on to develop type 2 diabetes, the large number of people with prediabetes worldwide implies a reservoir of new type 2 diabetes cases to come.

Optimising the management of prediabetes, with the aim of delaying diabetes onset for as long as possible, is therefore an urgent global clinical priority. Lifestyle interventions have been shown to be effective in diabetes prevention in several large clinical trials, and are effective in subjects who comply with the intervention.

Moreover, we know that the effectiveness of a lifestyle intervention increases in line with the number of lifestyle goals achieved. In the Diabetes Prevention Study DPS , for example, no patient who achieved at least four of the five lifestyle goals weight reduction, total fat intake, saturated fat intake, fibre intake, exercise went on to develop diabetes during the period of follow-up [ 70 ].

Thus, subjects at risk of diabetes should be counselled on improving their lifestyle, as is the case for patients with a diagnosis of type 2 diabetes.

However, weight loss arising from intensive lifestyle interventions is notoriously difficult to maintain over the long term, as shown by experience from the DPP, DPS and a number of other studies [ 19 , 69 , 70 , , ]. For this reason, current guidelines for the management of type 2 diabetes proposed jointly by the European Association for the Study of Diabetes and American Diabetes Association support the use of pharmacologic antidiabetic therapy usually metformin immediately after the diagnosis of diabetes for patients considered unlikely to benefit sufficiently from lifestyle intervention alone [ ].

Clinical experience with metformin from large, randomised clinical trials supports the efficacy of metformin in diabetes prevention, especially among younger, heavier subjects.

Importantly, these studies and five decades of clinical use in diabetes have established the relatively benign tolerability and acceptable safety profiles of metformin [ 60 ]. If experimental findings that are of potential relevance to the cardiovascular protection afforded by metformin are confirmed to be of clinical relevance, such as reduced levels of advanced glycation end-products or interference with cellular atherogenic processes see Sect.

Nevertheless, the gastrointestinal side effects of metformin can be troublesome and more than twice as many events occurred in the metformin versus placebo groups in the DPP 78 vs. Adherence to metformin was only slightly lower than adherence to placebo in the DPP 72 vs. The potential impact of vitamin B 12 depletion in prediabetic subjects will also require careful consideration.

The use of metformin in diabetes prevention is cost effective according to usual health economic criteria. In contrast, tolerability or safety issues may complicate the potential for the routine use, for diabetes prevention, of other agents shown to prevent or delay diabetes in the clinical trial setting, namely thiazolidinediones oedema, increased cardiovascular risk, fractures , acarbose high rate of discontinuation for gastrointestinal side effects , or basal insulin hypoglycaemia [ — ].

Newer, incretin-based therapies may hold potential for diabetes prevention but their evidence base is currently lacking [ ].

These agents must overcome current safety concerns relating to pancreatitis and pancreatic cancer before they can be considered for routine use in patients with early dysglycaemia [ ].

Metformin remains at the head of management algorithms for type 2 diabetes but the timing of its introduction within the course of dysglycaemia remains a matter for debate.

The introduction of metformin could be merely masking the diagnosis of diabetes by reducing blood glucose, and evidence of improved long-term outcomes in metformin-treated people with prediabetes is required. This need is emphasised by the reluctance of regulators to consider conversion to diabetes as a genuine clinical outcome, with prevention or delay of its onset considered an unambiguous clinical benefit in its own right.

A diagnosis of diabetes carries a social stigma, and people diagnosed with diabetes may face a lifetime of higher costs for, or reduced access to, health insurance, and limited access to certain professions [ , ].

There remains a strong case for intervention to prevent conversion of prediabetes to clinical type 2 diabetes, which is recognised in current management guidelines. A substantial proportion of subjects with prediabetes are likely to benefit from a combination of lifestyle intervention and pharmacologic intervention to prevent or delay the onset of type 2 diabetes.

The current evidence base supports a role for metformin in diabetes prevention, combined with counselling, to achieve a healthier lifestyle. International Diabetes Federation. Complications of diabetes. Accessed Jan American Diabetes Association.

Economic costs of diabetes in the U. in Diabetes Care. PubMed Central Google Scholar. World Health Organization. Diabetes: the cost of diabetes. Standards of medical care in diabetes— Google Scholar. Merlotti C, Morabito A, Pontiroli AE.

Prevention of type 2 diabetes: a systematic review and meta-analysis of different intervention strategies. Diabetes Obes Metab. CAS PubMed Google Scholar. DeFronzo RA, Bonnadonna RC, Ferrannini E. Pathogenesis of NIDDM. A balanced overview. DeFronzo RA. Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidaemia and atherosclerosis.

Neth J Med. Nathan DM, Davidson MB, DeFronzo RA, Heine RJ, Henry RR, Pratley R, et al. Impaired fasting glucose and impaired glucose tolerance: implications for care. Buysschaert M, Bergman M. Definition of prediabetes. Med Clin North Am. Rydén L, Grant PJ, Anker SD, Berne C, Cosentino F, Danchin N, et al.

ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the task force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology ESC and developed in collaboration with the European Association for the Study of Diabetes EASD.

Eur Heart J. PubMed Google Scholar. Genuth S, Alberti KG, Bennett P, Buse J, Defronzo R, Kahn R, et al. Follow-up report on the diagnosis of diabetes mellitus.

World Health Organization: Definition, diagnosis and classification of diabetes mellitus and its complications. Report of a WHO Consultation. Part 1: diagnosis and classification of diabetes mellitus. Geneva: World Health Organization; Mann DM, Carson AP, Shimbo D, Fonseca V, Fox CS, Muntner P.

Impact of A1C screening criterion on the diagnosis of pre-diabetes among U. PubMed Central PubMed Google Scholar. Cohen RM, Haggerty S, Herman H. HbA1c for the diagnosis of diabetes and prediabetes: is it time for a mid-course correction? J Clin Endocrinol Metab. CAS PubMed Central PubMed Google Scholar.

DeFronzo RA, Eldor R, Abdul-Ghani M. Pathophysiologic approach to therapy in patients with newly diagnosed type 2 diabetes.

Rhee MK, Herrick K, Ziemer DC, Vaccarino V, Weintraub WS, Narayan KM, et al. Many Americans have prediabetes and should be considered for metformin therapy. Ziegler D, Rathmann W, Dickhaus T, Meisinger C, Mielck A.

International Diabetes Federation Diabetes Atlas. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. Ramachandran A, Arun N, Shetty AS, Snehalatha C.

Efficacy of primary prevention interventions when fasting and postglucose dysglycemia coexist: analysis of the Indian Diabetes Prevention Programmes IDPP-1 and IDPP Cheng YJ, Gregg EW, Geiss LS, Imperatore G, Williams DE, Zhang X, et al.

No drug references linked in this topic. Find in topic Formulary Print Share. View in. Language Chinese English. Author: R Paul Robertson, MD Section Editor: David M Nathan, MD Deputy Editor: Katya Rubinow, MD Literature review current through: Jan This topic last updated: Dec 19, Although the lifetime risk of type 2 diabetes is high, our ability to predict and prevent type 2 diabetes in the general population is challenging.

However, individuals at high risk, including those with impaired fasting glucose IFG , impaired glucose tolerance IGT , obesity, close relatives with type 2 diabetes, or who are members of certain ethnic groups Asian, Hispanic, African American , are appropriate candidates for preventive interventions [ 1 ].

Moreover, genetic risk factors for type 2 diabetes have increasingly been identified, and polygenic risk scores may enhance the traditional demographic and clinical risk factor stratification in the future [ 2 ].

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Mayo Clinic offers appointments Anthocyanins in raspberries Arizona, Florida Diaebtes Minnesota and at Prevvention Clinic Health System locations. Lifestyle choices, including Anthocyanins in raspberries a healthy Meication, exercising and staying at a healthy weight, are key to managing type 2 diabetes. But you also might need to take medication to keep your blood sugar, also called glucose, at a healthy level. Sometimes one medication is enough. In other cases, taking several medications works better. The list of medications for type 2 diabetes is long and can be confusing. Recent Diabeges Beetroot juice for inflammation medicatiln types Anthocyanins in raspberries medifation medications, and most Americans living Diabetes prevention through medication type 2 diabetes are eligible. Inthe American Diabetes Association ADA Beetroot juice for inflammation the European Association for thgough Study of Diabetes EASD jointly released new medication recommendations for adults with type Occupational injury prevention diabetes. Macronutrient Balancing Strategies recommended newer types of Diaetes medications as first-line treatment for adults with type 2 diabetes who also have a type of heart disease called atherosclerotic cardiovascular disease ASCVDheart failure, kidney disease, or have a high risk for ASCVD. New research from CDC examined how many US adults with type 2 diabetes would meet the recommended criteria to use these medications, which are classified as glucagon-like peptide-1 receptor agonists GLP-1s and sodium-glucose cotransporter 2 inhibitors SGLT-2s. This study showed that more than 8 in 10 US adults with type 2 diabetes are eligible, per updated guidelines, for new, effective diabetes medicines. These medicines are not just beneficial for blood sugar management but also help reduce risk for diabetes complications.

Diabetes prevention through medication -

Skip directly to site content Skip directly to search. Español Other Languages. Use of New Diabetes Medicines. Minus Related Pages. New medicines can help manage type 2 diabetes, and most adults are eligible.

Learn More. Recommended and Prevalent Use of Glucagon-like Peptide-1 Receptor Agonists and Sodium—Glucose Cotransporter-2 Inhibitors in a National Population-Based Sample Annals of Internal Medicine acpjournals.

org Find out more about type 2 diabetes More Research Summaries. Last Reviewed: June 26, Source: Centers for Disease Control and Prevention. Facebook Twitter LinkedIn Syndicate. home Diabetes Home. To receive updates about diabetes topics, enter your email address: Email Address.

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Lifestyle choices, including eating a healthy diet, exercising and staying at a healthy weight, are key to managing type 2 diabetes. But you also might need to take medication to keep your blood sugar, also called glucose, at a healthy level.

Sometimes one medication is enough. In other cases, taking several medications works better. The list of medications for type 2 diabetes is long and can be confusing. Take time to learn about these medicines — how they're taken, what they do and what side effects they may cause.

That can help you get ready to talk to your health care provider about diabetes treatment choices that are right for you. Several classes of type 2 diabetes medicines exist. Each class of medicine works in a different way to lower blood sugar.

A medication may work by:. Each class of medicine has one or more medications. Some of these medications are taken by mouth, while others must be taken as a shot. Below is a list of common diabetes medications. Other medications are available too. Ask your health care provider about your choices and the pros and cons of each.

People with liver problems or a history of heart failure shouldn't take this kind of diabetes medicine. No one diabetes treatment is best for everyone.

What works for one person may not work for another. Your health care provider can explain how one medication or multiple medications may fit into your diabetes treatment plan. Sometimes combining medicines may increase the effectiveness of each individual medicine to lower blood sugar.

Talk to your provider about the pros and cons of specific diabetes medications for you. There is a problem with information submitted for this request. Sign up for free and stay up to date on research advancements, health tips, current health topics, and expertise on managing health.

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Products and services. Diabetes treatment: Medications for type 2 diabetes By Mayo Clinic Staff. Thank you for subscribing! Sorry something went wrong with your subscription Please, try again in a couple of minutes Retry. Show references Papadakis MA, et al. Diabetes mellitus and hypoglycemia.

McGraw-Hill; Accessed Sept. Wexler DJ. Overview of general medical care in nonpregnant adults with diabetes mellitus. Oral medication: What are my options?

American Diabetes Association.

Throkgh prevention strategies for both type Beetroot juice for inflammation and type 2 diabetes should range from efforts ghrough on individuals identified preventon being at risk for developing diabetes to preveention Beetroot juice for inflammation and Digestive health benefits strategies. Prevention or delay in the onset Diabetes prevention through medication througy should not only alleviate the burden of the disease on the individual, but could also decrease the associated morbidity and mortality. Ideal prevention strategies would differ depending on the type of diabetes. Given its increasing incidence and prevalence, the development of safe and cost-effective interventions to reduce the risk of developing diabetes are urgently needed to decrease the burden on individuals and the health-care system. Type 1 diabetes is a chronic autoimmune condition characterized by destruction of pancreatic beta cells.