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Background <p>Type 2 diabetes mellitus (T2DM) is closely linked to obesity and carries a high risk of metabolic complications. While GLP-1 receptor agonists like dulaglutide improve blood sugar and support modest weight loss, many patients do not reach their treatment goals. Mazdutide, a dual GLP-1 and glucagon receptor agonist, may offer stronger metabolic benefits.</p> Objective <p>To compare the efficacy and safety of mazdutide versus dulaglutide in adults with T2DM.</p> Methods <p>We systematically reviewed randomized controlled trials comparing mazdutide and dulaglutide. Primary outcomes included changes in HbA1c, body weight, and achievement of glycemic and weight-loss targets. Safety outcomes included treatment-emergent adverse events. Data were pooled using random-effects models, and evidence certainty was assessed using GRADE.</p> Results <p>Three trials met inclusion criteria. Mazdutide led to greater reductions in HbA1c (− 0.25%) and body weight (− 2.97&#xa0;kg) compared with dulaglutide. Patients were more likely to achieve HbA1c &lt; 7.0%, ≥ 5% weight loss, and the combined target of ≥ 5% weight loss with HbA1c &lt; 7.0%. Fasting plasma glucose was numerically but not significantly improved. Mazdutide was associated with higher rates of gastrointestinal side effects and decreased appetite, with a non-significant numerical increase in hypoglycemia, while serious adverse events and discontinuations were similar between treatments. Glycemic and major weight outcomes were supported by high-certainty evidence; most safety outcomes were moderate-certainty.</p> Conclusions <p>Mazdutide, based on evidence from three RCTs, provides preliminary evidence of meaningful improvements in blood sugar control and weight loss compared with dulaglutide, though with an increased risk of mostly manageable gastrointestinal effects; given the limited number of trials, these findings should be considered preliminary and supporting its potential role as a promising dual-action therapy for T2DM management, pending confirmation in larger, longer-term trials.</p> Graphical abstract <p></p>

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Efficacy and safety of mazdutide vs. dulaglutide in adults with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月24日

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  • Muhammad Hassan,
  • Muhammad Hussain,
  • Saifullah Khan,
  • Muhammad Tayyab Azam,
  • Zain Ul Abideen Shahid,
  • Abdul Hannan,
  • Muhammad Mussawir Khuhro,
  • Sahil Bhagia,
  • Hasibullah Aminpoor

摘要

Background

Type 2 diabetes mellitus (T2DM) is closely linked to obesity and carries a high risk of metabolic complications. While GLP-1 receptor agonists like dulaglutide improve blood sugar and support modest weight loss, many patients do not reach their treatment goals. Mazdutide, a dual GLP-1 and glucagon receptor agonist, may offer stronger metabolic benefits.

Objective

To compare the efficacy and safety of mazdutide versus dulaglutide in adults with T2DM.

Methods

We systematically reviewed randomized controlled trials comparing mazdutide and dulaglutide. Primary outcomes included changes in HbA1c, body weight, and achievement of glycemic and weight-loss targets. Safety outcomes included treatment-emergent adverse events. Data were pooled using random-effects models, and evidence certainty was assessed using GRADE.

Results

Three trials met inclusion criteria. Mazdutide led to greater reductions in HbA1c (− 0.25%) and body weight (− 2.97 kg) compared with dulaglutide. Patients were more likely to achieve HbA1c < 7.0%, ≥ 5% weight loss, and the combined target of ≥ 5% weight loss with HbA1c < 7.0%. Fasting plasma glucose was numerically but not significantly improved. Mazdutide was associated with higher rates of gastrointestinal side effects and decreased appetite, with a non-significant numerical increase in hypoglycemia, while serious adverse events and discontinuations were similar between treatments. Glycemic and major weight outcomes were supported by high-certainty evidence; most safety outcomes were moderate-certainty.

Conclusions

Mazdutide, based on evidence from three RCTs, provides preliminary evidence of meaningful improvements in blood sugar control and weight loss compared with dulaglutide, though with an increased risk of mostly manageable gastrointestinal effects; given the limited number of trials, these findings should be considered preliminary and supporting its potential role as a promising dual-action therapy for T2DM management, pending confirmation in larger, longer-term trials.

Graphical abstract