Diabetes Research and Clinical Practice: Published on July, 2022

The American Diabetes Association recommends that metformin should be started at the time of type 2 diabetes mellitus (T2DM) diagnosis, unless there are contraindications. Metformin is safe, effective, economic, and might reduce the risk of cardiovascular events and death. When glycemic goals are not achieved with metformin monotherapy, stepwise addition of other antidiabetic drugs to metformin is suggested.

However, many T2DM patients fail to achieve glycemic goals with initial metformin monotherapy and, of those who achieve current goals, few consistently maintain these targets over 3 years [3]. Indeed, some studies suggest that timely glycemic control during the early stage of T2DM may improve long-term glycemic durability and reduce long-term risk of diabetic complications and mortality.

Antidiabetic drugs with a low risk of hypoglycemia are generally preferable for combination antidiabetic drug regimen with metformin for patients with untreated T2DM.

TAKE-HOME MESSAGE

This meta-analysis of randomized controlled trials compared the effectiveness of glycemic control and hypoglycemia risk of combination therapy versus standard metformin therapy in patients with untreated type 2 diabetes.

The current meta-analysis, comprising 14 randomized controlled trials with > 5000 patients with untreated T2DM, revealed that combination therapy with metformin plus either DPP4i, SGLT2i, or pioglitazone vs. metformin monotherapy was associated with half a percent reduction of HbA1c, 0.92 mmol/L reduction in FPG, and a higher proportion of patients achieving HbA1c < 7% after ≥ 24 weeks of treatment.

The pooled results showed that combination therapy was associated with reduced HbA1c and fasting plasma glucose compared with metformin monotherapy. However, the incidence of hypoglycemia was not different between the two groups.

Conclusions

This meta-analysis suggests initial combination therapy with metformin plus a low hypoglycemic risk antidiabetic drug (e.g. DPP4i, SGLT2i or pioglitazone), compared to metformin monotherapy, provides benefits in glycemic control and does not increase a risk of hypoglycemia in patients with untreated T2DM.

The benefit of combination therapy was consistent across different races, baseline body weight, baseline HbA1c and disease duration.

These findings suggest that a combination of metformin and a low hypoglycemic risk antidiabetic drug can demonstrate better glycemic control without hypoglycemia in this patient population.

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