Editor’s Perspective

May delivers a particularly rich set of updates across metabolic and endocrine medicine. Highlights include new cardiorenal data on tirzepatide in type 2 diabetes, long-term weight-loss maintenance strategies in obesity, the emergence of oral orforglipron as a post-injectable maintenance option, renewed evidence for fenofibrate in diabetic retinopathy, and a landmark global consensus renaming PCOS as Polyendocrine Metabolic Ovarian Syndrome (PMOS). Together, these studies underscore the shift toward chronic-disease frameworks, organ protection beyond glycaemia, and precision in how we name and classify endocrine conditions.

Research Highlights

1. Tirzepatide vs Dulaglutide: Kidney Outcomes — SURPASS-CVOT

Study Focus:

Comparison of tirzepatide and dulaglutide on major kidney outcomes in adults with type 2 diabetes and established ASCVD, including albuminuria, eGFR decline, and composite renal endpoints across CKD risk categories.

Key Findings:

• Tirzepatide reduced the composite kidney outcome by 23% compared with dulaglutide.
• Benefits were consistent across low–moderate and high-risk CKD groups.
• In low–moderate CKD, the benefit was driven by lower incidence of new macroalbuminuria.
• In high-risk CKD, the dominant effect was slower eGFR decline, with a between-group difference of 0.93 mL/min/1.73 m² per year.
• Overall annual eGFR decline was significantly slower with tirzepatide.
• GI adverse events were more frequent but consistent with the incretin class profile.

Clinical Takeaway:

Tirzepatide demonstrates meaningful renal protection beyond glycaemic control, reinforcing its role as a cardiorenal-metabolic therapy rather than a glucose-lowering agent alone.

2. Long-Term Weight-Loss Maintenance With Tirzepatide — SURMOUNT-MAINTAIN

Study Focus:

Randomised evaluation of whether continuing tirzepatide at maximum tolerated dose (MTD), reducing to 5 mg, or switching to placebo best maintains weight loss achieved during a 60-week open-label tirzepatide phase.

Key Findings:

• Continuing MTD maintained the greatest weight reduction (–21.9%).
• Dose reduction to 5 mg preserved substantial benefit (–16.6%).
• Switching to placebo resulted in significant regain (–9.9%).
• Rescue therapy required in 8% (MTD), 25% (5 mg), and 67% (placebo).
• Cardiometabolic markers remained stable or improved with continued tirzepatide but worsened with placebo.

Clinical Takeaway:

Obesity is a chronic disease requiring ongoing pharmacotherapy. Continued tirzepatide is optimal; dose reduction remains a clinically viable compromise where tolerability, cost, or patient preference warrant adjustment.

3. Oral Orforglipron for Weight-Loss Maintenance After Injectables — ATTAIN-MAINTAIN

Study Focus:

Evaluation of whether switching from injectable tirzepatide or semaglutide to oral orforglipron can sustain weight loss and cardiometabolic improvements achieved during SURMOUNT-5.

Key Findings:

• In the tirzepatide cohort, 74.7% of weight loss was maintained with orforglipron vs 49.2% with placebo.
• In the semaglutide cohort, 79.3% was maintained vs 37.6% with placebo.
• Cardiometabolic markers (HbA1c, fasting glucose, lipids, BP, waist circumference) remained stable with orforglipron but deteriorated with placebo.
• GI adverse events were the most common, generally mild-to-moderate.

Clinical Takeaway:

Orforglipron offers a scalable oral maintenance strategy for patients who prefer to discontinue injectables, expanding long-term obesity management options and potentially improving adherence.

4. Fenofibrate and Diabetic Retinopathy Progression — LENS Trial

Study Focus:

Randomised trial assessing whether fenofibrate slows progression of diabetic retinopathy and reduces the need for ophthalmic intervention in adults with diabetes.

Key Findings:

• Fenofibrate reduced retinopathy progression compared with placebo.
• Fewer participants required laser or intravitreal therapy.
• Benefits were most pronounced in those with early or moderate retinopathy.
• Safety profile was consistent with prior fenofibrate studies.

Clinical Takeaway:

Fenofibrate remains a valuable adjunct in selected patients with early diabetic retinopathy, complementing glycaemic and blood pressure optimisation.

5. Global Renaming of PCOS: Adoption of “Polyendocrine Metabolic Ovarian Syndrome (PMOS)”

Study Focus:

International consensus process to develop a scientifically accurate, culturally appropriate, stigma-reducing, and globally implementable replacement name for PCOS.

Key Findings:

• Over 14,000 patients and clinicians participated across surveys and workshops.
• Strong consensus that “PCOS” is inaccurate, misleading, and contributes to stigma and diagnostic delay.
• Preferred terminology emphasised endocrine, metabolic, and ovarian components.
• Agreed new name: Polyendocrine Metabolic Ovarian Syndrome (PMOS).
• Global implementation strategy underway, including guideline updates, ICD coding changes, and education campaigns.

Clinical Takeaway:

PMOS better reflects the condition’s multisystem pathophysiology, improves clinician–patient communication, and supports earlier recognition. Progressive adoption across clinical, research, and policy environments is anticipated.

For Further Reading

• SURPASS-CVOT Kidney Outcomes: https://doi.org/10.1016/S2213-8587(26)00032-X
• SURMOUNT-MAINTAIN: https://doi.org/10.1016/S0140-6736(26)00656-2
• ATTAIN-MAINTAIN: https://doi.org/10.1038/s41591-026-04386-7
• LENS Trial: https://doi.org/10.3310/AAPH5610
• PMOS Global Consensus: https://doi.org/10.1016/S0140-6736(26)00717-8

Closing Note

This month’s updates reinforce a recurring theme: endocrine therapeutics are increasingly defined by organ protection, chronic-disease management, and precision in classification. As the evidence base expands, structured evaluation and personalised, mechanism-based care remain central to improving patient outcomes.

Dr Tejhmal Rehman
Editor of PES Monthly Endocrine Round-Up
MRCP(UK), MRCP(Endo), FRCP(London), EBEEDM, CCT(UK)
Consultant Endocrinologist
Executive Member, Pakistan Endocrine Society

Dr Ali Asghar
MRCP(UK), FACE, FRCP(Edin), FRCP(London)
Consultant Endocrinologist
President, Pakistan Endocrine Society

Disclaimer: This newsletter provides educational commentary on recent endocrine literature and does not replace clinical judgment or local guidelines.