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Polyagonists in Type 2 Diabetes Management

  • REVIEW
  • Published:
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Abstract

Purpose of the Review

This review summarizes the new developments in polyagonist pharmacotherapy for type 2 diabetes.

Recent Findings

Several dual- and triple-agonists targeting different pathogenic pathways of type 2 diabetes have entered clinical trials and have led to significant improvements in glycaemia, body weight, fatty liver, and cardio-renal risk factors, with variable adverse event profiles but no new serious safety concerns. Combining agents with complementary and synergistic mechanisms of action have enhanced efficacy and safety. Targeting multiple pathogenic pathways simultaneously has led to enhanced benefits which potentially match those of bariatric surgery. Tirzepatide, cotadutide, BI456906, ritatrutide, and CagriSema have entered phase 3 clinical trials. Outcomes from published clinical studies are reviewed. Efficacy-safety profiles are heterogeneous between agents, suggesting the potential application of precision medicine and need for personalized approach in pharmacological management of type 2 diabetes and obesity.

Summary

Polyagonism has become a key strategy to address the complex pathogenesis of type 2 diabetes and co-morbidities and increasing number of agents are moving through clinical trials. Heterogeneity in efficacy-safety profiles calls for application of precision medicine and need for judicious personalization of care.

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Abbreviations

ALT:

Alanine transaminase

AST:

Aspartate aminotransferase

CCK:

Cholecystokinin

CCKR:

Cholecystokinin receptor

CI:

Confidence interval

CKD:

Chronic kidney disease

DACRA:

Dual amylin calcitonin receptor agonists

DBP:

Diastolic blood pressure

GCGR:

Glucagon receptor

GIP:

Glucose-dependent insulinotropic peptide

GIPR:

GIP receptor

GLP-1:

Glucagon-like peptide

GLP-1R:

Glucagon-like peptide receptor

GLP-1-RA:

GLP-1 receptor agonist

HFpEF:

Heart failure with preserved ejection fraction

HR:

Hazard ratio

hsCRP:

High sensitivity C-reactive protein

LDL:

Low density lipoprotein

MACE:

Major adverse cardiovascular events

NASH:

Non-alcoholic steatohepatitis

OR:

Odds ratio

RCT:

Randomized controlled trial

SBP:

Systolic blood pressure

SD:

Standard deviation

T2D:

Type 2 diabetes

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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  1. Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka

    H. A. Dissanayake

  2. Hormone Centre, The Central Hospital, Colombo, Sri Lanka

    N. P. Somasundaram

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NPS developed the research question, search strategy and outline of the review article and critically reviewed the manuscript . HAD conducted the literature review, wrote the first draft of the manuscript, prepared tables and figures. Both authors read the submitted manuscript.

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Dissanayake, H.A., Somasundaram, N.P. Polyagonists in Type 2 Diabetes Management. Curr Diab Rep 24, 1–12 (2024). https://doi.org/10.1007/s11892-023-01530-2

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