Editor’s Perspective

April brings a diverse set of clinically relevant updates across endocrine practice, including new evidence on levothyroxine dosing flexibility, the largest UK trial to date evaluating CGM in type 2 diabetes on modern therapies, long‑term metabolic risk associated with early‑life obesity, and the impact of chronic TSH suppression on menopause‑related health in women with differentiated thyroid carcinoma. Together, these studies reinforce the importance of personalised, risk‑stratified care across thyroid, metabolic, and renal endocrinology.

Research Highlights

1. Fasting vs Nonfasting, Dose‑Adjusted Levothyroxine Ingestion — Randomized Clinical Trial

Study Focus:

Evaluation of whether levothyroxine taken with breakfast (with a 15% dose increase) maintains biochemical stability compared with traditional fasting ingestion.

Key Messages:

• TSH stability was equivalent between fasting and nonfasting groups (≈74% in both).
• Free T4 and total T3 levels were also similar.
• Patients reported better well‑being and strong preference for nonfasting intake.
• ~89% chose to continue nonfasting LT4 at study end.
• No safety concerns identified.

Clinical Takeaway:

A modest 15% dose increase allows levothyroxine to be taken with breakfast without compromising biochemical control, improving convenience and patient satisfaction.

2. Continuous Glucose Monitoring vs SMBG in Type 2 Diabetes — FreeDM2 Randomised Trial

Study Focus:

Large UK multicentre RCT evaluating real‑time CGM versus SMBG in adults with type 2 diabetes treated with basal insulin plus SGLT2 inhibitors and/or GLP‑1 or dual GIP/GLP‑1 receptor agonists.

Key Findings:

• Baseline HbA1c: 8.8% in both groups.
• At 16 weeks: CGM 8.0% vs SMBG 8.7% (difference –0.6%; p<0.0001).
• At 32 weeks: CGM 7.8% vs SMBG 8.3% (difference –0.5%; p<0.0001).
• Early improvements occurred during self‑management despite similar insulin dose changes.
• CGM users showed healthier dietary choices and higher physical activity.
• No increase in hypoglycaemia; two severe episodes occurred only in SMBG group.
• CGM adherence was excellent (median 97–98%).

Clinical Takeaway:

Real‑time CGM significantly improves HbA1c, time‑in‑range, and self‑management behaviours in adults with type 2 diabetes on basal insulin plus modern therapies, supporting wider adoption in routine care.

3. Weight Trajectories, Obesity Onset (17–60 Years), and Cause‑Specific Mortality — ODDS Pooled Cohort Study

Study Focus:

Swedish pooled cohort assessing how weight gain patterns and age of obesity onset influence long‑term mortality.

Key Findings:

• Median weight gain from 17–60 years was 0.42 kg/year.
• Early obesity onset (17–29 years) markedly increased all‑cause mortality (HR ~1.7).
• Rapid early‑adult weight gain increased mortality from cardiovascular disease, cancers, diabetes, digestive and renal disease.
• Later‑life weight gain showed weaker associations.
• Longer exposure to metabolic stress likely drives risk.

Clinical Takeaway:

Preventing early‑adult weight gain is critical, as obesity before age 30 confers the highest long‑term mortality risk.

3. Menopause‑Related Health Outcomes in Women with Differentiated Thyroid Carcinoma on Long‑Term TSH Suppression

Thyroid (ATA), 2026

Study Focus:

Assessment of how long‑term TSH suppression after total thyroidectomy affects menopause‑related health outcomes in women with differentiated thyroid carcinoma (DTC).

Key Findings:

• Chronic suppression worsened vasomotor symptoms (hot flashes, sleep disturbance).
• Lower bone mineral density and higher rates of osteopenia/osteoporosis were observed, especially post‑
• Mild cardiovascular effects consistent with subclinical hyperthyroidism (higher resting heart rate, atrial ectopy).
• Quality‑of‑life scores reflected greater fatigue, anxiety, and thermoregulatory symptoms.
• Relaxing suppression in low‑risk women did not increase recurrence risk.

Clinical Takeaway:

Long‑term TSH suppression can exacerbate menopause‑related symptoms and negatively impact bone and cardiovascular health. These findings support risk‑stratified TSH targets, especially once patients transition to low‑risk disease status.

Review Article of the Month

GLP‑1 Receptor Agonists in Chronic Kidney Disease — Current Insights and Future Directions

Key Insights:

• GLP‑1RAs provide renal benefits beyond glycaemic control, including reduced albuminuria and slower eGFR decline.
• Effects appear additive to SGLT2 inhibitors.
• Semaglutide now shows slowed CKD progression and reduced mortality in diabetic CKD.
• Mechanisms include reduced inflammation, oxidative stress, fibrosis, and improved endothelial function.
• Future directions: use in non‑diabetic CKD and evaluation of dual/triple incretin agonists.

Clinical Takeaway:

GLP‑1RAs are becoming a key therapeutic class in CKD management, with expanding roles beyond diabetes as evidence grows.

For Further Reading

• Fasting vs Nonfasting Levothyroxine Trial: https://doi.org/10.1210/clinem/dgaf686
• ODDS Cohort Study (Weight Trajectories & Mortality): https://doi.org/10.1016/j.eclinm.2026.103870
• FreeDM2 Trial: CGM vs SMBG in Type 2 Diabetes: https://doi.org/10.1016/S2213-8587(26)00076-8
• Menopause‑Related Outcomes in DTC on Long‑Term TSH Suppression: https://doi.org/10.1177/10507256261442839
• GLP‑1RA Review in CKD: https://doi.org/10.2147/IJNRD.S522424

Closing Note
April’s studies reinforce the importance of early metabolic intervention, patient‑centred dosing strategies, and the expanding therapeutic reach of incretin‑based agents. As evidence evolves, integrated endocrine‑renal care continues to gain prominence.

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.