Quiz Ref ID Epidemiologic studies^1,2 have demonstrated an association between poor glycemic control and microvascular complications in patients with type 2 diabetes mellitus (T2DM). Randomized controlled trials^3-5 have demonstrated that intensive glycemic control reduces albuminuria. Less clear, however, is whether intensive glycemic control prevents clinical renal end points (eg, progressive decrease in glomerular filtration rate) beyond albuminuria in patients with T2DM. Despite the lack of strong evidence, expert panels and guidelines continue to recommend a target hemoglobin A_1c (HbA_1c) of less than 7.0% for prevention of renal disease and other microvascular complications. Quiz Ref ID The 2007 National Kidney Foundation Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease (CKD)⁶ endorse intensive glycemic control, and these recommendations are reinforced by the 2011 American Diabetes Association guidelines.⁷ As stated in the guidelines, recommendations for intensive glycemic control for prevention of renal disease are based on studies that have demonstrated an improvement in albuminuria, a surrogate end point.

Context: Concomitant obesity is common among patients with type 1 diabetes mellitus (T1DM), yet adjunctive therapy options are scarce. Objective: We assess the efficacy and adverse outcomes of glucagon-like peptide 1 (GLP-1) analogues when used as adjunctive therapy for T1DM. Method: PubMed, EMBASE, Cochrane Central, and Scopus databases were searched for randomized controlled trials up to December 2022. Efficacy outcomes were A1c level, body weight, and total daily insulin (TDI) after ≥12 weeks of GLP-1 therapy. We also assessed 12 different adverse outcomes. Subgroup analysis was done for newly diagnosed or C-peptide positive (C-pos) patients. We report the certainty of evidence based on the GRADE assessment tool. Results: A total of 24 studies using 4 different GLP-1 analogues with a total of 3377 patients were included. Liraglutide had the most substantial evidence with effect sizes on A1c (−0.09%/mg), weight (−2.2 kg/mg), and TDI (−4.32 IU/mg). Liraglutide dose was the greatest predictor of greater average weight loss and TDI decrease but was associated with higher odds of nausea (OR 6.5; 95% CI, 5.0-8.4) and ketosis (OR 1.8; 95% CI, 1.1-2.8). Odds of severe (OR 0.67; 95% CI, 0.43-1.04) or symptomatic hypoglycemia (OR 0.89; 95% CI, 0.53-1.51) were not significantly elevated. Among C-pos patients, greater A1c decrease (−0.51% vs −0.28%) but similar weight loss and TDI were seen. Effect sizes for exenatide were similar, but studies had higher risk of bias and safety data were sparse. Conclusion: Our meta-analysis supports therapeutic benefits of liraglutide for patients with T1DM mainly for weight loss and insulin dose reduction. Newly diagnosed or C-pos patients do not appear to experience greater weight loss benefits.