Adding metformin to insulin therapy in patients with type 2 diabetes does not impact long-term outcomes

The addition of metformin to insulin therapy in patients with type 2 diabetes does not significantly impact all-cause or cardiovascular mortality, although the combination reduced hemoglobin A1C values, weight gain, and insulin doses, a recent study found. Combining metformin to insulin also may increase the risk of hypoglycemia.

According to the World Diabetes Foundation, India has the world’s largest diabetic population, estimated at 50.8 million people. Worldwide, diabetes is one of the leading causes of premature illness and death.

Researchers from Denmark conducted a systematic review and meta-analysis that evaluated the efficacy and safety of combining the oral antihyperglycemic agent metformin with insulin compared with[s2If !is_user_logged_in()]…

[/s2If][s2If is_user_logged_in()] insulin therapy alone. Randomized controlled trials that enrolled patients with type 2 diabetes that were of at least 12 weeks’ duration were included in the analysis. Many outcomes were evaluated, including all-cause mortality, cardiovascular mortality, micro- and macrovascular complications, hypoglycemia, quality of life, insulin dose, glycemic control, and weight.

Key Point: The addition of metformin to insulin therapy in patients with type 2 diabetes does not impact all-cause mortality or cardiovascular mortality, although the risk of severe hypoglycemia may be increased. Of benefit, patients taking the combination may have improved hemoglobin A1c values, require less insulin, and have a reduced body weight.

A total of 26 trials were included overall, representing more than 2,000 patients. The average daily dose of metformin ranged from 1,000 mg to 2,550 mg, and the insulin regimens varied considerably. In most trials, patients were not naïve to metformin or insulin therapy. The investigators concluded that all trials had a high risk of bias due to inadequacies in randomization, allocation concealment, blinding, and funding disclosure.

The addition of metformin to insulin did not significantly impact the risk of all-cause mortality or cardiovascular mortality. Mixed results were obtained for hypoglycemia, with one statistical model suggesting no difference, while another suggested increased risk of severe hypoglycemia (relative risk, 2.83). There was no significant difference in mild hypoglycemia.

Insulin doses were significantly reduced in patients receiving combination therapy vs insulin alone (mean difference of -18.65 units per day), although the difference was less profound in patients with a body mass index (BMI) of less than 30 vs patients with a higher BMI (mean difference of -13.36 units per day compared with -21.76 units per day). Patients taking the combination also had a reduced hemoglobin A1C value (mean difference of -0.60%), BMI (mean difference -1.27), and weight (mean difference -1.68 kg).

Total adverse events were not significantly impacted and quality of life could not be evaluated due to a lack of enough trials reporting this outcome. Although details were not reported, the investigators stated that there were no differences in micro- or macrovascular complications in the few trials that reported such data.

Source: Hemmingsen B, Christensen LL, Wetterslev J, et al. Comparison of metformin and insulin versus insulin alone for type 2 diabetes: A systematic review of randomized clinical trials with meta-analyses and trial sequential analysis. BMJ. 2012;344:e1771.

Diabetes Facts. World Diabetes Foundation. Available at: Accessed May 16 , 2012.

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This entry was posted in Diabetes, Non-Communicable Disease, Pharmacology, Primary Care and tagged , , , , , , , , . Volume: .

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