1. Compared to other anti-diabetic regimens, patients treated with a GLP-1 agonist and basal insulin combination had a greater mean reduction of HbA1c levels.

2. The GLP-1 agonist and basal insulin combination was associated with significant weight loss in study participants.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Type 2 diabetes is associated with significant mortality and morbidity, including cardiac, renal, vascular, and neurologic complications. While there are many available treatment regimens, each is associated with significant adverse profiles – the most significant adverse effect is hypoglycemia associated with insulin and insulin secretagogues, which limits how aggressive clinicians can be in assisting patients to reach their HbA1c targets. Glucagon-like peptide-1 (GLP-1) receptor agonist, as an incretin mimetic, increases insulin secretion only in the presence of increased blood glucose. As such, GLP-1 agonists are not associated with significant risks of hypoglycemia. Results of a meta-analysis published today in the Lancet showed that the combination of GLP-1 agonist and basal insulin was more effective at lowering HbA1c levels than other regimens, was not associated with increased risks of hypoglycemia, and was associated with significant weight loss in study subjects. The meta-analysis included 15 studies with over 4,000 participants. Between-study heterogeneity were noted and could moderately limit the power of certain conclusions drawn from this meta-analysis.

Click to read the study, published today in The Lancet

Relevant Reading: Type 2 diabetes across generations: from pathophysiology to prevention and management

In-Depth [meta-analysis]: This is a meta-analysis that included 15 studies with 4348 participants. The outcomes assessed were the following: change in HbA1c between baseline and end of intervention, proportion of participants achieving an HbA1c of 7.0% or lower at the end of the study period, and the number of participants with hypoglycemic episodes.

In a pooled analysis of all 15 trials, the GLP-1 agonist/basal insulin combination resulted in a greater mean reduction in HbA1c than with any other treatment strategy by 0.44% (95% confidence interval, CI, 0.60 to 0.29 reduction). The Egger test showed publication bias (p=0.0047); however, further trim-and-fill analysis showed that this bias did not impact the estimates. There was no significant between-study heterogeneity.

In a pooled analysis of 14 studies, there was a higher likelihood of participants achieving an HbA1c level of 7.0% or lower at the end of the intervention with GLP-1 agonist and basal insulin combination (absolute risk difference, 17.4%) compared with other treatments. There was statistically significant between-study heterogeneity. There was no apparent publication bias (p=0.16).

A pooled analysis of 11 studies showed no significant difference in the relative risk of developing hypoglycemia between GLP-1 agonist/basal insulin combination and other treatments. There was statistically significant between-study heterogeneity and no significant publication bias (p=0.81).

Finally, a pooled analysis of 12 studies showed that GLP-1 agonist with basal insulin treatment led to a greater mean reduction in weight compared to other treatments (-3.22 kg, 95% CI, -4.90 to -1.54), with statistically significant between-study heterogeneity. There was no publication bias detected (p=0.81).

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