Efficacy and Safety of Retatrutide in the Treatment of Diabetes and/or Obesity Comorbid with Chronic Kidney disease: a Systematic Review and Meta-Analysis.
This systematic review and meta-analysis evaluated the efficacy and safety of retatrutide — a novel triple agonist (GIP/GLP-1/glucagon receptor) — specifically in patients with type 2 diabetes and/or obesity comorbid with chronic kidney disease (CKD). Researchers conducted a comprehensive literature search and ultimately included eight randomized controlled trials. The study found that retatrutide was associated with a statistically significant mean reduction in HbA1c of -1.04% (95% CI: -1.42 to -0.67) and body weight reductions of up to -24.2%. A subgroup analysis suggested a dose-dependent pattern in glycemic outcomes, with lower doses appearing to produce greater HbA1c reductions than higher doses, though this finding warrants cautious interpretation. Secondary analyses indicated possible renoprotective effects, reflected by reductions in albuminuria. Gastrointestinal adverse events were the most commonly reported safety concern, consistent with the broader drug class. Key limitations include the small number of included studies (n=8), potential heterogeneity across trials, and the fact that CKD-specific data may have been drawn from subgroup analyses of broader trials rather than CKD-dedicated studies. The overall evidence base for retatrutide in CKD patients remains early-stage.
Why this grade: Although this is a meta-analysis of RCTs in humans — generally a high-evidence design — the grade is moderated to moderate-human due to the small number of included studies (n=8), likely reliance on CKD subgroup data from broader trials rather than CKD-dedicated RCTs, and the relatively early clinical evidence base for retatrutide.
There are still substantial clinical challenges in treating patients who come with type 2 diabetes and/or obesity in addition to chronic kidney disease (CKD). Retatrutide, an innovative agent, represents a potential advancement in therapy; however, its performance and safety profile specifically in a CKD population are not fully determined yet. This meta-analysis and systematic review sought to consolidate existing research on the use of retatrutide in this comorbid patient group. A comprehensive literature search identified relevant randomized controlled trials for inclusion. Reductions in glycated hemoglobin (HbA1c) and body weight were the primary goals for evaluating effectiveness, whereas adverse events were used to evaluate safety. Eight studies were included in the present research work. A significant mean reduction in HbA1c of -1.04% (95% CI -1.42 to -0.67) and a noticeable loss in weight, reaching up to -24.2%, were both linked with retatrutide treatment. A subgroup analysis indicated that the glycemic benefits were dose-dependent, with lower doses (≤8 mg) demonstrating a greater HbA1c reduction (-1.39%) than higher doses (≥12 mg, -0.65%). Furthermore, secondary analyses pointed toward possible renoprotective effects, evidenced by a reduction in albuminuria. The safety profile is primarily characterized by gastrointestinal adverse events, which is anticipated for this drug class. In conclusion, retatrutide exhibits strong efficacy for improving glucose levels and promoting weight loss in patients with diabetes, obesity and CKD, displaying a distinctive dose-response pattern where lower doses may be more effective for glycemic control. Its potential for kidney protection is promising, though clinicians should be mindful of managing gastrointestinal tolerability.
Educational summary of published research — not medical advice. Full text is shown only where licensing permits.