Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: systematic review and network meta-analysis

Jan 29, 2024BMJ (Clinical research ed.)

GLP-1 drugs' effects on blood sugar, weight, and fat levels in type 2 diabetes

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Abstract

76 trials involving 39,246 participants were evaluated to assess the efficacy and safety of glucagon-like peptide-1 receptor agonists in adults with type 2 diabetes.

All 15 glucagon-like peptide-1 receptor agonists effectively lowered haemoglobin A1c and fasting plasma glucose concentrations compared to placebo.
Tirzepatide produced the largest reduction in haemoglobin A1c (-2.10%) and fasting plasma glucose (-3.12 mmol/L), indicating superior glycaemic control.
CagriSema led to the greatest weight loss (-14.03 kg), followed by tirzepatide (-8.47 kg), demonstrating significant benefits for weight management.
Semaglutide was effective in reducing low-density lipoprotein and total cholesterol levels.
Gastrointestinal adverse events associated with glucagon-like peptide-1 receptor agonists raise safety concerns, particularly at higher doses.

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OBJECTIVE: To evaluate the comparative efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on glycaemic control, body weight, and lipid profile in adults with type 2 diabetes.

DESIGN: Systematic review and network meta-analysis.

DATA SOURCES: PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase from database inception to 19 August 2023.

ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Eligible randomised controlled trials enrolled adults with type 2 diabetes who received GLP-1RA treatments and compared effects with placebo or any GLP-1RA drug, with a follow-up duration of at least 12 weeks. Trials with a crossover design, non-inferiority studies comparing GLP-1RA and other drug classes without a placebo group, using withdrawn drugs, and non-English studies were deemed ineligible.

RESULTS: 76 eligible trials involving 15 GLP-1RA drugs and 39 246 participants were included in this network meta-analysis; all subsequent estimates refer to the comparison with placebo. All 15 GLP-1RAs effectively lowered haemoglobin Aand fasting plasma glucose concentrations. Tirzepatide induced the largest reduction of haemoglobin Aconcentrations (mean difference -2.10% (95% confidence interval -2.47% to -1.74%), surface under the cumulative ranking curve 94.2%; high confidence of evidence), and fasting plasma glucose concentrations (-3.12 mmol/L (-3.59 to -2.66), 97.2%; high confidence), and proved the most effective GLP-1RA drug for glycaemic control. Furthermore, GLP-1RAs were shown to have strong benefits to weight management for patients with type 2 diabetes. CagriSema (semaglutide with cagrilintide) resulted in the highest weight loss (mean difference -14.03 kg (95% confidence interval -17.05 to -11.00); high confidence of evidence), followed by tirzepatide (-8.47 kg (-9.68 to -7.26); high confidence). Semaglutide was effective in lowering the concentration of low density lipoprotein (-0.16 mmol/L (-0.30 to -0.02)) and total cholesterol (-0.48 mmol/L (-0.84 to -0.11)). Moreover, this study also raises awareness of gastrointestinal adverse events induced by GLP-1RAs, and concerns about safety are especially warranted for high dose administration. 1c1c

CONCLUSIONS: GLP-1RAs are efficacious in treating adults with type 2 diabetes. Compared with the placebo, tirzepatide was the most effective GLP-1RA drug for glycaemic control by reducing haemoglobin Aand fasting plasma glucose concentrations. GLP-1RAs also significantly improved weight management for type 2 diabetes, with CagriSema performing the best for weight loss. The results prompt safety concerns for GLP-1RAs, especially with high dose administration, regarding gastrointestinal adverse events. 1c

SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022342845.

Key numbers

2.10%

HbA Reduction

Mean difference compared to

14.03 kg

Weight Loss

Mean difference compared to

2.86

Safety Concern Odds Ratio

Odds ratio for discontinuation due to adverse events

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Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: systematic review and network meta-analysis

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