Metformin Monotherapy for Type 2 Diabetes Mellitus

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.

The following decision support rules contain links to this evidence summary:

• Metformin as a primary choice for an oral hypoglycemic agent http://www.ebmeds.org/ebmeds/ebmeds_home.asp?mode=scripts&submode=view&id=scr00016&country=UK

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]