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Evidence summaries

Metformin Monotherapy for Type 2 Diabetes Mellitus

Metformin monotherapy in type 2 diabetes is effective for glycaemic control and protection of major cardiovascular events, and beneficial for weight, lipids, insulinaemia and diastolic blood pressure. Level of evidence: "A"

A systematic review and meta-analysis 3 assessing effects of metformin monotherapy on glycemic control and weight in drug-naive patients with type 2 diabetes mellitus (T2DM) included 16 studies (n=1140). Compared to placebo, metformin monotherapy was associated with decreased glycosated hemoglobin (HbA1c) by 0.95% at 3 months (95% CI 0.50 to 1.39; I²=87%) and 1.32% at 6 months (95% CI 1.01 to 1.62; I²=71%), and decreased fasting plasma glucose by 1.92mmol/L at 1 month (95% CI 0.11 to 3.74, I²=88%), 1.79mmol/L at 3 months (95% CI 0.92 to 2.66, I²=88%) and 2.14mmol/L at 6 months (95% CI 1.17 to 3.12; I²=82%). No significant difference was demonstrated for the comparisons of weight due to relatively small number of studies retrieved.

Another meta-analysis 4 estimating the relative efficacy and safety associated with glucose-lowering drugs included 301 trials (1 417 367 patient-months). Compared with metformin, sulfonylurea (standardized mean difference [SMD] 0.18, 95% CI 0.01 to 0.34), thiazolidinedione (SMD 0.16, 95% CI, 0.00 to 0.31), DPP-4 inhibitor (SMD 0.33, 95% CI 0.13 to 0.52), and α-glucosidase inhibitor (SMD 0.35, 95% CI 0.12 to 0.58) monotherapy were associated with higher HbA1C levels. .

A Cochrane review [Abstract] 1 included 18 studies with 10 680 participants. Metformin was compared with sulphonylureas (7 trials), dipeptidyl peptidase-4 inhibitors (3), glucagon-like peptide-1 analogue (1), thiazolidinediones (7), insulin (2), meglitinides (1). No trial compared metformin with placebo or a behaviour changing interventions. There was no clear evidence whether metformin monotherapy compared with other glucose-lowering drugs influenced patient-important outcomes in short term (1 to 4 years).

Authors' conclusion: Metformin may be the first therapeutic option in the diabetes mellitus type 2 with overweight or obesity, as it may prevent some vascular complications, and mortality. Sulphonylureas, alpha-glucosidase inhibitors, thiazolidinediones, meglitinides, insulin, and diet fail to show more benefit for glycaemia control, body weight, or lipids, than metformin.

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    References

    • Gnesin F, Thuesen ACB, Kähler LKA et al. Metformin monotherapy for adults with type 2 diabetes mellitus. Cochrane Database Syst Rev 2020;(6):CD012906. [PubMed]
    • Piera-Mardemootoo C, Lambert P, Faillie JL. Efficacy of metformin on glycemic control and weight in drug-naive type 2 diabetes mellitus patients: A systematic review and meta-analysis of placebo-controlled randomized trials. Therapie 2018;(Epub ahead of print). [PubMed]
    • Palmer SC, Mavridis D, Nicolucci A et al. Comparison of Clinical Outcomes and Adverse Events Associated With Glucose-Lowering Drugs in Patients With Type 2 Diabetes: A Meta-analysis. JAMA 2016;316(3):313-24. [PubMed]

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