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Review of Metformin Use for Type 2 Diabetes Prevention.

ABSTRACT: CONTEXT:Prediabetes is prevalent and significantly increases lifetime risk of progression to type 2 diabetes. This review summarizes the evidence surrounding metformin use for type 2 diabetes prevention. EVIDENCE ACQUISITION:Articles published between 1998 and 2017 examining metformin use for the primary indication of diabetes prevention available on MEDLINE. EVIDENCE SYNTHESIS:Forty articles met inclusion criteria and were summarized into four general categories: (1) RCTs of metformin use for diabetes prevention (n=7 and n=2 follow-up analyses); (2) observational analyses examining metformin use in heterogeneous subgroups of patients with prediabetes (n=9 from the Diabetes Prevention Program, n=1 from the biguanides and the prevention of the risk of obesity [BIGPRO] trial); (3) observational analyses examining cost effectiveness of metformin use for diabetes prevention (n=11 from the Diabetes Prevention Program, n=1 from the Indian Diabetes Prevention Program); and (4) real-world assessments of metformin eligibility or use for diabetes prevention (n=9). Metformin was associated with reduced relative risk of incident diabetes, with the strongest evidence for use in those at highest risk (i.e., aged <60 years, BMI ?35, and women with histories of gestational diabetes). Metformin was also deemed cost effective in 11 economic analyses. Recent studies highlighted low rates of metformin use for diabetes prevention in real-world settings. CONCLUSIONS:Two decades of evidence support metformin use for diabetes prevention among higher-risk patients. However, metformin is not widely used in real-world practice, and enhancing the translation of this evidence to real-world practice has important implications for patients, providers, and payers.

SUBMITTER: Moin T

PROVIDER: S-EPMC6613947 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Review of Metformin Use for Type 2 Diabetes Prevention.

Moin Tannaz T Schmittdiel Julie A JA Flory James H JH Yeh Jessica J Karter Andrew J AJ Kruge Lydia E LE Schillinger Dean D Mangione Carol M CM Herman William H WH Walker Elizabeth A EA

American journal of preventive medicine 20180817 4

<h4>Context</h4>Prediabetes is prevalent and significantly increases lifetime risk of progression to type 2 diabetes. This review summarizes the evidence surrounding metformin use for type 2 diabetes prevention.<h4>Evidence acquisition</h4>Articles published between 1998 and 2017 examining metformin use for the primary indication of diabetes prevention available on MEDLINE.<h4>Evidence synthesis</h4>Forty articles met inclusion criteria and were summarized into four general categories: (1) RCTs ...[more]

PMID: 30126667

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Project description:The largest and longest clinical trial of metformin for the prevention of diabetes is the Diabetes Prevention Program/Diabetes Prevention Program Outcomes Study (DPP/DPPOS). In this review, we summarise data from the DPP/DPPOS, focusing on metformin for diabetes prevention, as well as its long-term glycaemic and cardiometabolic effects and safety in people at high-risk of developing diabetes. The DPP (1996-2001) was a RCT of 3234 adults who, at baseline, were at high-risk of developing diabetes. Participants were assigned to masked placebo (n = 1082) or metformin (n = 1073) 850 mg twice daily, or intensive lifestyle intervention (n = 1079). The masked metformin/placebo intervention phase ended approximately 1 year ahead of schedule because of demonstrated efficacy. Primary outcome was reported at 2.8 years. At the end of the DPP, all participants were offered lifestyle education and 88% (n = 2776) of the surviving DPP cohort continued follow-up in the DPPOS. Participants originally assigned to metformin continued to receive metformin, unmasked. The DPP/DPPOS cohort has now been followed for over 15 years with prospective assessment of glycaemic, cardiometabolic, health economic and safety outcomes. After an average follow-up of 2.8 years, metformin reduced the incidence of diabetes by 31% compared with placebo, with a greater effect in those who were more obese, had a higher fasting glucose or a history of gestational diabetes. The DPPOS addressed the longer-term effects of metformin, showing a risk reduction of 18% over 10 and 15 years post-randomisation. Metformin treatment for diabetes prevention was estimated to be cost-saving. At 15 years, lack of progression to diabetes was associated with a 28% lower risk of microvascular complications across treatment arms, a reduction that was no different among treatment groups. Recent findings suggest metformin may reduce atherosclerosis development in men. Originally used for the treatment of type 2 diabetes, metformin, now proven to prevent or delay diabetes, may serve as an important tool in battling the growing diabetes epidemic. Long-term follow-up, currently underway in the DPP/DPPOS, is now evaluating metformin's potential role, when started early in the spectrum of dysglycaemia, on later-stage comorbidities, including cardiovascular disease and cancer.Trial registrationClinicalTrials.gov NCT00038727 and NCT00004992.

Project description:Background: Metformin, a commonly used antidiabetic medication, is available in both an immediate-release (IR) formulation and a long-acting formulation (metformin extended-release; XR). Objective: We performed a systematic review to compare the effectiveness, safety, and patient compliance and satisfaction between the metformin IR and XR formulations. Method: We searched for randomized control trials (RCTs) and observational studies comparing the effectiveness, safety, or patient compliance and satisfaction of metformin XR with metformin IR using the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases. Following report screening, data collection, and risk of bias assessment, we separately pooled data from RCTs and observational studies using the Grading of Recommendation Assessment, Development, and Evaluation approach to rate the quality of evidence. Result: We included five RCTs, comprising a total of 1,662 patients, and one observational study, comprising 10,909 patients. In the meta-analyses, no differences were identified in outcomes of effectiveness and safety between the two forms of metformin (including change in HbA1c: mean difference (MD), 0.04%, 95% confidence interval [CI], -0.05-0.13%, fasting blood glucose: MD, -0.03 mmol/L, 95% CI, -0.22-0.15 mmol/L, postprandial blood glucose: MD, 0.50 mmol/L, 95% CI, -0.71-1.72 mmol/L, adverse events of abdominal pain: relative risk (RR), 1.15, 95% CI, 0.57-2.33, all-cause death (RR, 3.02, 95% CI 0.12-73.85), any adverse events (RR, 1.14, 95% CI 0.97-1.34), any adverse events leading to treatment discontinuation: RR, 1.51, 95% CI, 0.82-2.8, any gastrointestinal adverse events: RR, 1.09, 95% CI, 0.93-1.29, diarrhea: RR, 0.82, 95% CI, 0.53-1.27, flatulence: RR, 0.43, 95% CI, 0.15-1.23, nausea: RR, 0.97, 95% CI, 0.64-1.47, severe adverse events: RR, 0.64, 95% CI, 0.28-1.42, and vomiting: RR, 1.46, 95% CI, 0.6-3.56). Data from both the RCTs and the observational study indicate mildly superior patient compliance with metformin XR use compared with metformin IR use; this result was attributable to the preference for once-daily administration with metformin XR. Conclusion: Our systematic review indicates that metformin XR and IR formulations have similar effectiveness and safety, but that metformin XR is associated with improved compliance to treatment.

Project description:BackgroundType 2 diabetes (T2D) has been associated with increased breast cancer risk, but commonly prescribed antidiabetic medications such as metformin may reduce risk. Few studies have investigated T2D and medications together in relation to breast cancer.Patients and methodsData came from 44 541 Sister Study participants aged 35 to 74 years at enrollment (2003-2009) who satisfied eligibility criteria, followed through 15 September 2017. Information on time-varying, self-reported, physician-diagnosed, prevalent and incident T2D, use of antidiabetic medications, and covariates was obtained from baseline and follow-up questionnaires. Incident breast cancers were confirmed with medical records. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated.ResultsDuring follow-up (median, 8.6 years), 2678 breast cancers were diagnosed at least 1 year after enrollment. There were 3227 women (7.2%) with prevalent and 2389 (5.3%) with incident T2D, among whom 61% (n = 3386) were ever treated with metformin. There was no overall association between T2D and breast cancer risk (HR 0.99; 95% CI, 0.87-1.13). However, T2D was associated with increased risk of triple-negative breast cancer (HR 1.40; 95% CI, 0.90-2.16). Compared with not having T2D, T2D with metformin use was not associated with overall breast cancer risk (HR 0.98; 95% CI, 0.83-1.15), but it was associated with decreased risk of estrogen receptor (ER)-positive breast cancer (HR 0.86; 95% CI 0.70-1.05) and increased risk of ER-negative (HR 1.25; 95% CI, 0.84-1.88) and triple-negative breast cancer (HR 1.74; 95% CI, 1.06-2.83). The inverse association with ER-positive cancer was stronger for longer duration (≥10 year) metformin use (HR 0.62; 95% CI, 0.38-1.01; P for trend = 0.09). Results were supported by sensitivity analyses.ConclusionOur findings suggest that associations between T2D and breast cancer may differ by hormone receptor status and that associations between T2D and ER-positive breast cancer may be reduced by long-term metformin use.

Project description:ImportanceMetformin is widely viewed as the best initial pharmacological option to lower glucose concentrations in patients with type 2 diabetes mellitus. However, the drug is contraindicated in many individuals with impaired kidney function because of concerns of lactic acidosis.ObjectiveTo assess the risk of lactic acidosis associated with metformin use in individuals with impaired kidney function.Evidence acquisitionIn July 2014, we searched the MEDLINE and Cochrane databases for English-language articles pertaining to metformin, kidney disease, and lactic acidosis in humans between 1950 and June 2014. We excluded reviews, letters, editorials, case reports, small case series, and manuscripts that did not directly pertain to the topic area or that met other exclusion criteria. Of an original 818 articles, 65 were included in this review, including pharmacokinetic/metabolic studies, large case series, retrospective studies, meta-analyses, and a clinical trial.ResultsAlthough metformin is renally cleared, drug levels generally remain within the therapeutic range and lactate concentrations are not substantially increased when used in patients with mild to moderate chronic kidney disease (estimated glomerular filtration rates, 30-60 mL/min per 1.73 m2). The overall incidence of lactic acidosis in metformin users varies across studies from approximately 3 per 100,000 person-years to 10 per 100,000 person-years and is generally indistinguishable from the background rate in the overall population with diabetes. Data suggesting an increased risk of lactic acidosis in metformin-treated patients with chronic kidney disease are limited, and no randomized controlled trials have been conducted to test the safety of metformin in patients with significantly impaired kidney function. Population-based studies demonstrate that metformin may be prescribed counter to prevailing guidelines suggesting a renal risk in up to 1 in 4 patients with type 2 diabetes mellitus--use which, in most reports, has not been associated with increased rates of lactic acidosis. Observational studies suggest a potential benefit from metformin on macrovascular outcomes, even in patients with prevalent renal contraindications for its use.Conclusions and relevanceAvailable evidence supports cautious expansion of metformin use in patients with mild to moderate chronic kidney disease, as defined by estimated glomerular filtration rate, with appropriate dosage reductions and careful follow-up of kidney function.

Project description:BackgroundPrevious evidence yielded contradictory findings on the relationship between metformin and anemia. This study aims to assess whether metformin use is associated with iron-deficiency anemia (IDA) risk in patients with type 2 diabetes (T2D) in Beijing, China.MethodsOverall, 60,327 newly diagnosed T2D patients were included based on a historical cohort study design. The information pertaining to these patients was gathered from the Beijing Medical Claim Data for Employees Database. These patients were then categorized into the metformin and non-metformin groups and matched on a 1:1 propensity score based on their initial antidiabetic prescription. The Cox proportional hazards models were utilized to calculate the incidences and the hazard ratios (HRs).ResultsThe study enrolled 27,960 patients with type 2 diabetes, with 13,980 patients in each of the initial glucose-lowering prescription groups: metformin and non-metformin. During a median follow-up period of 4.84 years, 4832 patients developed IDA. The incidence of IDA was significantly lower in the metformin group (26.08/1000 person-years) than in the non-metformin group (43.20/1000 person-years). Among the three groups divided by the proportion of days covered by metformin, we found a negative correlation between the proportion of days covered by metformin and the risk of IDA. The risk of IDA in patients with a proportion of days covered by metformin of <20%, 20-79%, and ≥80% was 0.43 (0.38, 0.48), 0.37 (0.34, 0.42), and 0.91 (0.85, 0.98), respectively, compared to the non-metformin group. We also performed subgroup analyses and sensitivity analyses: the incidence of IDA in the metformin group was lower than that in the non-metformin group in all subgroups, and the protective effect was more significant in subgroups of patients aged ≥65, with Charlson comorbidity index (CCI) ≥2, and with gastric acid inhibitor use.ConclusionsIn Chinese patients with T2DM, metformin treatment was associated with a decreased risk of IDA admission, and this risk responded positively to the proportion of days covered by metformin. These findings suggest that metformin may have a pleiotropic effect on IDA in patients with type 2 diabetes. Our study has important clinical implications for the management of patients with diabetes and other conditions that increase the risk of IDA.

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Review of Metformin Use for Type 2 Diabetes Prevention.

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Review of Metformin Use for Type 2 Diabetes Prevention.

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