Publications
Stay up to date with our literature reviews which are curated by experts to feature the most important publications released each month. Explore our publications for access to concise summary slides for your own use.
Tirzepatide after Intensive Lifestyle Intervention in Adults with Overweight or Obesity: the SURMOUNT-3 Phase 3 Trial
Nat Med. 2023; online ahead of print DOI: 10.1038/s41591-023-02597-w
The use of antiobesity medications following intensive lifestyle intervention has been proposed as a strategy to induce additional weight reduction (which may be needed to achieve optimal control of obesity-related complications) or, at a minimum, to prevent weight regain. The effects of tirzepatide, the dual GIP and GLP-1RA, on weight reduction after successful intensive lifestyle intervention are unknown.
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Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity
N Engl J Med. 2023; DOI: 10.1056/NEJMoa2302392
Orforglipron is a once-daily oral nonpeptide GLP-1RA in development for weight management and the treatment of T2D. This phase 2 double-blind trial evaluated the efficacy and safety of orforglipron in adults with obesity, or with overweight plus at least one weight-related coexisting condition, and without T2D. In total, 272 participants were randomised to orforglipron (12, 24, 36 or 45 mg) or placebo once daily for 36 weeks, with a primary endpoint of change from baseline in body weight at week 26.
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Albuminuria-Lowering Effect of Adding Semaglutide on Top of Empagliflozin in Individuals with Type 2 Diabetes: A Randomized and Placebo-Controlled Study
Diabetes Obes Metab. 2023; online ahead of print DOI: 10.1111/dom.15287
The proposed different mechanisms of SGLT2i and GLP-1RAs indicate that combination therapy may have additive or synergistic effects on the kidneys. This placebo-controlled, double-blind, parallel-group study investigated the effect on albuminuria of adding semaglutide to ongoing treatment with empagliflozin compared with empagliflozin alone in 60 individuals with T2D and albuminuria.
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Effect of Semaglutide versus Other Glucagon-Like Peptide-1 Receptor Agonists on Cardio-Metabolic Risk Factors in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Head-to-Head, Phase 3, Randomized Controlled Trials
J Diabetes Complications. 2023;37:108529 DOI: 10.1016/j.jdiacomp.2023.108529
GLP-1RAs vary in their abilities to control glycaemia, reduce body weight and improve other cardiometabolic risk factors. A recent systematic review and meta-analysis assessed the efficacy and safety of semaglutide compared with other GLP-1RAs in head-to-head phase 3 RCTs in adults with T2D.
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Oral Semaglutide 50 mg Taken Once per Day in Adults with Overweight or Obesity (OASIS 1): a Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial
Lancet. 2023. DOI: 10.1016/S0140-6736(23)01185-6
Oral semaglutide 7 mg and 14 mg once-daily are approved for the treatment of T2D and improve glycaemic control with accompanying body weight reductions. A higher dose of once-daily oral semaglutide 50 mg is currently being investigated for the treatment of obesity in people with overweight or obesity, and for glycaemic control in people with T2D. The OASIS 1 trial assessed once-daily oral semaglutide 50 mg in adults with overweight or obesity, without T2D.
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Efficacy and Safety of Oral Orforglipron in Patients with Type 2 Diabetes: A Multicentre, Randomised, Dose-Response, Phase 2 Study
Lancet. 2023. DOI: 10.1016/S0140-6736(23)01302-8
Orforglipron, an oral, non-peptide GLP-1RA, was assessed at various once-daily doses (3 mg, 12 mg, 24 mg, 36 mg, 45 mg) and dose-escalation schedules vs placebo and dulaglutide in 383 patients with T2D, with or without metformin, and BMI ≥23 kg/m2, with no food or water restrictions.
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Efficacy and Safety of Co-Administered Once-weekly Cagrilintide 2.4 mg with Once-Weekly Semaglutide 2.4 mg in Type 2 Diabetes: a Multicentre, Randomised, Double-Blind, Active-Controlled, Phase 2 Trial
Lancet. 2023. DOI: 10.1016/ S0140-6736(23)01163-7
Combining the GLP-1 RA semaglutide with the long-acting amylin analogue cagrilintide has been shown to have weight-loss benefits. However, the impact of the combination of cagrilintide and semaglutide (CagriSema) on HbA1c is unknown. In a 32-week, double-blind, phase 2 trial, 92 adults with T2D and a BMI ≥27 kg/m2 on metformin, with or without an SGLT2i, were randomised to once-weekly subcutaneous CagriSema, semaglutide or cagrilintide (all escalated to 2.4 mg).
Benefits and Harms of Drug Treatment for Type 2 Diabetes: Systematic Review and Network Meta-Analysis of Randomised Controlled Trials
BMJ 2023;381:e074068 DOI 10.1136/bmj-2022-074068
Keeping abreast of the rising volume of randomized trials in adults with type 2 diabetes presents a formidable task. Recent randomized trials have shown cardiovascular and kidney advantages with finerenone, an innovative non-steroidal mineralocorticoid receptor antagonist, and weight loss with tirzepatide, a dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 (GLP-1) receptor agonist.
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GLP-1 Receptor Agonists and Risk ofAdverse Cerebrovascular Outcomes inType 2 Diabetes: A Systematic Reviewand Meta-Analysis of Randomized Controlled Trials
J Clin Endocrinol Metab. 2023; online ahead of print DOI: 10.1016/j.jacc.2022.07.021 10.1210/clinem/dgad076
Although the beneficial effects of GLP-1RAs on major cardiovascular events have been established in patients with T2D, their effects on cerebrovascular outcomes remain undetermined.