Glucagon-Like Peptide-1 Receptor Agonist and Basal Insulin Combination Treatment for the Management of Type 2 Diabetes: A Systematic Review and Meta-Analysis

Study Questions:

What is the effect of combination treatment with a glucagon-like peptide-1 (GLP-1) agonist and basal insulin on glycemic control, hypoglycemia, and weight gain in patients with type 2 diabetes?

Methods:

The investigators systematically searched PubMed, Embase, Cochrane, Web of Knowledge, FDA.gov, and ClinicalTrials.gov for randomized controlled trials (published between Jan. 1, 1950, and July 29, 2014; no language restrictions) comparing GLP-1 agonist and basal insulin combination treatment to other antidiabetic treatments. The main endpoints were glycemic control, hypoglycemia, and change in weight. They assessed pooled data by use of a random-effects model.

Results:

Of 2,905 identified studies, 15 were eligible and were included in the analysis (n = 4,348 participants). Compared with other antidiabetic treatments, GLP-1 agonist and basal insulin combination treatment yielded an improved mean reduction in glycated hemoglobin (HbA1c) of –0.44% (95% confidence interval [CI], –0.60 to –0.29), an improved likelihood of achieving the target HbA1c of 7.0% or lower (relative risk, 1.92; 95% CI, 1.43-2.56), no increased relative risk of hypoglycemia (0.99; 0.76-1.29), and a mean reduction in weight of –3.22 kg (–4.90 to –1.54). Furthermore, compared with basal-bolus insulin regimens, the combination treatment yielded a mean reduction in HbA1c of –0.1% (–0.17 to –0.02), with lower relative risk of hypoglycemia (0.67, 0.56-0.80), and reduction in mean weight (–5.66 kg; –9.8 to –1.51).

Conclusions:

The authors concluded that GLP-1 agonist and basal insulin combination treatment can enable achievement of the ideal trifecta in diabetic treatment: robust glycemic control with no increased hypoglycemia or weight gain.

Perspective:

The study reports that, compared with other antidiabetic treatments, combination treatment with a GLP-1 agonist and basal insulin can yield improved glycemic control, with no increase in hypoglycemia and a reduction in weight. Furthermore, compared with basal-bolus insulin regimens, this combination offers greater HbA1c reduction with lower risk of hypoglycemia and a reduction in weight. These data thus lend support to GLP-1 agonist and basal insulin combination treatment as a therapeutic strategy that can improve the management of type 2 diabetes. Additional prospective studies are needed to establish the optimal approach to the application of this treatment in practice, and to validate these results.

Keywords: Hemoglobin A, Glycosylated, Risk, Insulin, Long-Acting, Glucagon-Like Peptide 1, Diabetes Mellitus, Type 2, Hypoglycemic Agents, Confidence Intervals, Weight Gain, Hypoglycemia


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