This Week in Endocrinology — Oct 28, 2026
Generated Oct 29, 2026 · 11:34
The week's practice-changing Endocrinology research, summarized for clinicians.
If the audio fails to play, refresh the page to renew the link.
Get next week’s Endocrinology briefing — free.
In your podcast app, or readable in your inbox with the audio one tap away.
Retatrutide Once Weekly for Treatment of Obstructive Sleep Apnea.
In two phase 3 trials, once-weekly retatrutide cut apnea-hypopnea events substantially more than placebo over 80 weeks in adults with obesity-related sleep apnea, with or without type 2 diabetes.
New England Journal of Medicine · 2026 · PubMed
This week’s papers
- 01
Retatrutide Once Weekly for Treatment of Obstructive Sleep Apnea.
In two phase 3 trials, once-weekly retatrutide cut apnea-hypopnea events substantially more than placebo over 80 weeks in adults with obesity-related sleep apnea, with or without type 2 diabetes.
Grunstein RR et al. · New England Journal of Medicine · 2026
From the briefingThe headline comes from the New England Journal of Medicine, where Grunstein and colleagues report two phase 3 placebo-controlled trials of once-weekly retatrutide, the investigational triple agonist of the GIP, GLP-1 and glucagon receptors, in adults with moderate-to-severe obstructive sleep apnea and a body-mass index of at least 27 [1]. One trial enrolled 243 people without type 2 diabetes and the other 448 people with it, and baseline apnea severity was striking, averaging close to 60 events per hour. At 80 weeks, the 9 milligram dose reduced the apnea-hypopnea index by roughly 24 more events per hour than placebo in people without diabetes, and by roughly 14 more events per hour in those with diabetes; the 12 milligram dose performed similarly, and results held under an intention-to-treat analysis. Weight loss reached about 22 percent in the non-diabetic trial, and gastrointestinal effects were the most common adverse events. The smaller apnea response in diabetes mirrors the familiar pattern of attenuated weight loss in that population. These are industry-funded trials of a drug not yet approved, and many patients would still have residual apnea, so the result positions retatrutide as a disease-modifying option rather than a replacement for airway therapy.
If you only have time for one paper this week, make it the retatrutide sleep apnea trials in the New England Journal of Medicine [1]. They provide phase 3 evidence that a triple agonist can substantially reduce apnea severity in people with and without type 2 diabetes, reopening the question of where pharmacotherapy sits alongside airway treatment in obesity-related sleep apnea.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 02
A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Acmopatide (CT-868), a Fully Biased GLP-1/GIP Receptor Agonist, in Adults With Type 1 Diabetes and Overweight or Obesity.
In adults with type 1 diabetes and obesity, 16 weeks of acmopatide modestly lowered HbA1c, reduced weight by up to about 7 percent, and caused no ketoacidosis or severe hypoglycaemia.
Klein KR et al. · Diabetes Care · 2026
From the briefingDiabetes Care carries a very different incretin story from Klein and colleagues: a 16-week phase 2 trial of acmopatide, a signal-biased GLP-1 and GIP receptor agonist, in 111 adults with type 1 diabetes and overweight or obesity [2]. The glycaemic effect was modest, with the 4.1 milligram dose lowering HbA1c by about 0.3 percentage points more than placebo, a difference the authors describe as nominally significant, while weight fell by up to about 7 percent and insulin doses dropped. Importantly, no diabetic ketoacidosis or severe hypoglycaemia occurred, though a trial this small and short cannot rule those risks out. It adds to the case for adjunctive incretin therapy in adiposity-driven type 1 diabetes, but it is early-phase evidence.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 03
Target Trial of Semaglutide Versus Dulaglutide or Liraglutide in Patients Receiving Hemodialysis.
Among haemodialysis patients with diabetes, semaglutide was associated with lower mortality and hospitalization than dulaglutide, but showed no significant advantage over liraglutide in this observational target-trial emulation.
Le D et al. · Diabetes Care · 2026
From the briefingAlso in Diabetes Care, Le and colleagues emulated a target trial using United States Renal Data System and Medicare data, comparing semaglutide with dulaglutide or liraglutide in about 3,900 patients with diabetes on maintenance haemodialysis [3]. Semaglutide was associated with roughly an 18 percent lower risk of death on dialysis, with one-year mortality of about 11 percent versus 13 percent, along with a modest reduction in hospitalization and slightly greater weight loss. The advantage held against dulaglutide but was not statistically significant against liraglutide, which is why the authors frame semaglutide as possibly preferred over dulaglutide specifically. This is careful observational work, but residual confounding remains possible.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 04
Normal-BMI MASLD is Associated with Increased Mortality, Cardiovascular Events, Cancer and Lower GLP-1 Use.
Normal-weight steatotic liver disease carried roughly 70 percent higher mortality than obesity-associated disease in matched patients, yet incretin therapy was used far less despite association with better survival.
Casimiro I et al. · Journal of Clinical Endocrinology & Metabolism · 2026
From the briefingMeanwhile, in the Journal of Clinical Endocrinology and Metabolism, Casimiro and colleagues used the TriNetX network to compare normal-weight and overweight metabolic dysfunction-associated steatotic liver disease, using ethnicity-specific BMI thresholds and about 52,000 propensity-matched pairs [4]. Patients with normal-BMI disease had roughly 70 percent higher all-cause mortality despite a more favourable metabolic profile, with ethnicity-specific excesses in heart attack, stroke, kidney failure and some cancers. Incretin use was markedly lower in this group yet was associated with better survival. The study is retrospective and database-driven, so the survival association with incretins should be read as hypothesis-generating, but it challenges the assumption that lean patients with fatty liver are lower risk.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 05
Safety of Sodium-Glucose Cotransporter 2 Inhibitors in Older Adults With Type 2 Diabetes: A Cohort Study.
In adults aged 75 or older with type 2 diabetes, starting an SGLT2 inhibitor rather than a DPP-4 inhibitor showed no excess harm and lower acute kidney injury risk, though some estimates were imprecise.
Harbi H et al. · Diabetes Care · 2026
From the briefingIn Diabetes Care, Harbi and colleagues conducted an active-comparator new-user cohort study in British Columbia of adults aged 75 and older with type 2 diabetes, comparing about 5,000 people starting an SGLT2 inhibitor with about 1,300 starting a DPP-4 inhibitor [5]. SGLT2 inhibitor initiation was associated with about a quarter lower risk of acute kidney injury and modestly fewer hospitalizations, with no difference in infection. Rates of ketoacidosis, falls and fractures did not differ, but the authors are candid that those estimates were imprecise and compatible with both benefit and harm. The DPP-4 group was also older and included more women, a reminder that prescribers were already selecting patients. Within those limits, the study supports the view that advanced age alone does not signal excess harm from SGLT2 inhibitors.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 06
Long-term Glycemia and Risk of Death in Cystic Fibrosis-Related Diabetes: A UK Cystic Fibrosis Registry Study.
In cystic fibrosis-related diabetes, mortality rose stepwise with long-term HbA1c, nearly doubling above 69 mmol/mol compared with 42 or lower, independent of lung function and modulator use.
Adler AI et al. · Diabetes Care · 2026
From the briefingA registry analysis from Adler and colleagues, also in Diabetes Care, turns to cystic fibrosis-related diabetes [6]. Among 4,477 people in the United Kingdom Cystic Fibrosis Registry followed for over 31,000 person-years, 758 people died, and mortality rose stepwise with long-term HbA1c. Compared with an HbA1c at or below 42 millimoles per mole, mortality was about 40 percent higher even in the 42 to 53 range and nearly doubled above 69, after adjusting for lung function, BMI and modulator use. It is observational and cannot show that lowering HbA1c reduces mortality, but the gradient begins at levels many would consider acceptable.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 07
Palopegteriparatide in Adults With Hypoparathyroidism: 3.5-Year Results From the Phase 3 PaTHway Trial.
After three and a half years of palopegteriparatide, nearly all adults with hypoparathyroidism were free of conventional calcium and active vitamin D therapy, and 89 percent remained normocalcaemic.
Khan AA et al. · Journal of Clinical Endocrinology & Metabolism · 2026
From the briefingIn the Journal of Clinical Endocrinology and Metabolism, Khan and colleagues report three-and-a-half-year results from the phase 3 PaTHway trial of palopegteriparatide in 82 adults with hypoparathyroidism [7]. Of the 73 participants completing week 182, 96 percent no longer needed therapeutic calcium doses, every participant was free of active vitamin D, and 89 percent were normocalcaemic. Urine calcium normalised early and stayed normal, kidney function gains were preserved, and bone density Z-scores remained above zero. Long-term data rest on an open-label extension without a comparator, but the durability is notable for a condition long managed with calcium and calcitriol.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 08
Efficacy and Safety of Lonapegsomatropin in Children With Turner Syndrome: 52-Week Results From the New InsiGHTS Trial.
Once-weekly lonapegsomatropin produced one-year height velocity and safety comparable to daily somatropin in a small phase 2 trial of prepubertal girls with Turner syndrome.
Davis SM et al. · Journal of Clinical Endocrinology & Metabolism · 2026
From the briefingIn the same journal, Davis and colleagues report the phase 2 New InsiGHTS trial of once-weekly lonapegsomatropin in 49 prepubertal girls with Turner syndrome [8]. At one year, height velocity was about 9 centimetres per year with both the weekly prodrug and daily somatropin, with similar height gains and safety. It is a small dose-ranging study, not a confirmatory trial, but it supports continued development of weekly growth hormone in this condition, where injection burden can limit adherence.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 09
Debate: Level of TSH at which thyroid hormone replacement should be initiated in gestation.
Two experts dispute levothyroxine for pregnant women with TSH 2.5 to 10, contrasting individualized treatment against concerns about uncertain benefit and overtreatment after guidelines raised thresholds.
Maraka S, Bliddal S · Journal of Clinical Endocrinology & Metabolism · 2026
From the briefingThe Journal of Clinical Endocrinology and Metabolism hosts a debate between Maraka and Bliddal on levothyroxine in pregnancy [9]. Recent guidelines raised the treatment threshold, suggesting treatment for a TSH of 4.0 or above with normal thyroxine only in the first trimester, and recommending against treatment between 2.5 and 4.0. Bliddal argues that individualized treatment remains reasonable in selected women in that lower range, citing biological heterogeneity and the limits of fixed cut-offs, while Maraka argues against routine treatment given uncertain benefit and the risk of overtreatment. The debate makes clear that the evidence gap, not the guideline wording, drives the disagreement.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 10
Reappraising the safety of menopausal hormone therapy for women-implications for the clinic.
Menopausal hormone therapy has a favourable benefit-risk balance for healthy women starting before 60 or within ten years of menopause, with formulation and route influencing thrombotic and breast risk.
Hirschberg AL · Journal of Clinical Endocrinology & Metabolism · 2026
From the briefingRounding out the theme, Hirschberg reviews the safety history of menopausal hormone therapy, also in that journal [10]. The review traces how the Women's Health Initiative reshaped practice and how the timing hypothesis then reframed it, concluding that for healthy women starting before 60 or within ten years of menopause, the benefit-risk balance is favourable. It highlights lower venous thromboembolism risk with transdermal estradiol and a possibly more favourable breast profile with micronized progesterone or dydrogesterone, while noting that randomized evidence for the progestogen differences is still lacking.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
The full briefing
This AudioScholar briefing is generated by artificial intelligence for healthcare professionals and trainees. It is not medical advice.
Welcome to This Week in Endocrinology. This week we're covering 10 notable papers spanning the expanding reach of incretin-based therapies, drug safety and glycaemic risk in vulnerable diabetes populations, and hormone replacement across the lifespan, from childhood growth to pregnancy and menopause. Let's dive in.
Incretin-based drugs keep moving into new indications and new patient groups, and four papers this week test how far that reach extends. The headline comes from the New England Journal of Medicine, where Grunstein and colleagues report two phase 3 placebo-controlled trials of once-weekly retatrutide, the investigational triple agonist of the GIP, GLP-1 and glucagon receptors, in adults with moderate-to-severe obstructive sleep apnea and a body-mass index of at least 27 [1]. One trial enrolled 243 people without type 2 diabetes and the other 448 people with it, and baseline apnea severity was striking, averaging close to 60 events per hour. At 80 weeks, the 9 milligram dose reduced the apnea-hypopnea index by roughly 24 more events per hour than placebo in people without diabetes, and by roughly 14 more events per hour in those with diabetes; the 12 milligram dose performed similarly, and results held under an intention-to-treat analysis. Weight loss reached about 22 percent in the non-diabetic trial, and gastrointestinal effects were the most common adverse events. The smaller apnea response in diabetes mirrors the familiar pattern of attenuated weight loss in that population. These are industry-funded trials of a drug not yet approved, and many patients would still have residual apnea, so the result positions retatrutide as a disease-modifying option rather than a replacement for airway therapy. Diabetes Care carries a very different incretin story from Klein and colleagues: a 16-week phase 2 trial of acmopatide, a signal-biased GLP-1 and GIP receptor agonist, in 111 adults with type 1 diabetes and overweight or obesity [2]. The glycaemic effect was modest, with the 4.1 milligram dose lowering HbA1c by about 0.3 percentage points more than placebo, a difference the authors describe as nominally significant, while weight fell by up to about 7 percent and insulin doses dropped. Importantly, no diabetic ketoacidosis or severe hypoglycaemia occurred, though a trial this small and short cannot rule those risks out. It adds to the case for adjunctive incretin therapy in adiposity-driven type 1 diabetes, but it is early-phase evidence.
Two observational studies extend incretin questions to populations that trials rarely reach. Also in Diabetes Care, Le and colleagues emulated a target trial using United States Renal Data System and Medicare data, comparing semaglutide with dulaglutide or liraglutide in about 3,900 patients with diabetes on maintenance haemodialysis [3]. Semaglutide was associated with roughly an 18 percent lower risk of death on dialysis, with one-year mortality of about 11 percent versus 13 percent, along with a modest reduction in hospitalization and slightly greater weight loss. The advantage held against dulaglutide but was not statistically significant against liraglutide, which is why the authors frame semaglutide as possibly preferred over dulaglutide specifically. This is careful observational work, but residual confounding remains possible. Meanwhile, in the Journal of Clinical Endocrinology and Metabolism, Casimiro and colleagues used the TriNetX network to compare normal-weight and overweight metabolic dysfunction-associated steatotic liver disease, using ethnicity-specific BMI thresholds and about 52,000 propensity-matched pairs [4]. Patients with normal-BMI disease had roughly 70 percent higher all-cause mortality despite a more favourable metabolic profile, with ethnicity-specific excesses in heart attack, stroke, kidney failure and some cancers. Incretin use was markedly lower in this group yet was associated with better survival. The study is retrospective and database-driven, so the survival association with incretins should be read as hypothesis-generating, but it challenges the assumption that lean patients with fatty liver are lower risk.
The second theme is safety and glycaemic risk in diabetes populations that are often underrepresented in trials. In Diabetes Care, Harbi and colleagues conducted an active-comparator new-user cohort study in British Columbia of adults aged 75 and older with type 2 diabetes, comparing about 5,000 people starting an SGLT2 inhibitor with about 1,300 starting a DPP-4 inhibitor [5]. SGLT2 inhibitor initiation was associated with about a quarter lower risk of acute kidney injury and modestly fewer hospitalizations, with no difference in infection. Rates of ketoacidosis, falls and fractures did not differ, but the authors are candid that those estimates were imprecise and compatible with both benefit and harm. The DPP-4 group was also older and included more women, a reminder that prescribers were already selecting patients. Within those limits, the study supports the view that advanced age alone does not signal excess harm from SGLT2 inhibitors. A registry analysis from Adler and colleagues, also in Diabetes Care, turns to cystic fibrosis-related diabetes [6]. Among 4,477 people in the United Kingdom Cystic Fibrosis Registry followed for over 31,000 person-years, 758 people died, and mortality rose stepwise with long-term HbA1c. Compared with an HbA1c at or below 42 millimoles per mole, mortality was about 40 percent higher even in the 42 to 53 range and nearly doubled above 69, after adjusting for lung function, BMI and modulator use. It is observational and cannot show that lowering HbA1c reduces mortality, but the gradient begins at levels many would consider acceptable.
Our third theme is hormone replacement, where long-acting formulations and shifting thresholds are reshaping practice from childhood through menopause. In the Journal of Clinical Endocrinology and Metabolism, Khan and colleagues report three-and-a-half-year results from the phase 3 PaTHway trial of palopegteriparatide in 82 adults with hypoparathyroidism [7]. Of the 73 participants completing week 182, 96 percent no longer needed therapeutic calcium doses, every participant was free of active vitamin D, and 89 percent were normocalcaemic. Urine calcium normalised early and stayed normal, kidney function gains were preserved, and bone density Z-scores remained above zero. Long-term data rest on an open-label extension without a comparator, but the durability is notable for a condition long managed with calcium and calcitriol. In the same journal, Davis and colleagues report the phase 2 New InsiGHTS trial of once-weekly lonapegsomatropin in 49 prepubertal girls with Turner syndrome [8]. At one year, height velocity was about 9 centimetres per year with both the weekly prodrug and daily somatropin, with similar height gains and safety. It is a small dose-ranging study, not a confirmatory trial, but it supports continued development of weekly growth hormone in this condition, where injection burden can limit adherence.
Two papers revisit thresholds where guidance has shifted. The Journal of Clinical Endocrinology and Metabolism hosts a debate between Maraka and Bliddal on levothyroxine in pregnancy [9]. Recent guidelines raised the treatment threshold, suggesting treatment for a TSH of 4.0 or above with normal thyroxine only in the first trimester, and recommending against treatment between 2.5 and 4.0. Bliddal argues that individualized treatment remains reasonable in selected women in that lower range, citing biological heterogeneity and the limits of fixed cut-offs, while Maraka argues against routine treatment given uncertain benefit and the risk of overtreatment. The debate makes clear that the evidence gap, not the guideline wording, drives the disagreement. Rounding out the theme, Hirschberg reviews the safety history of menopausal hormone therapy, also in that journal [10]. The review traces how the Women's Health Initiative reshaped practice and how the timing hypothesis then reframed it, concluding that for healthy women starting before 60 or within ten years of menopause, the benefit-risk balance is favourable. It highlights lower venous thromboembolism risk with transdermal estradiol and a possibly more favourable breast profile with micronized progesterone or dydrogesterone, while noting that randomized evidence for the progestogen differences is still lacking.
If you only have time for one paper this week, make it the retatrutide sleep apnea trials in the New England Journal of Medicine [1]. They provide phase 3 evidence that a triple agonist can substantially reduce apnea severity in people with and without type 2 diabetes, reopening the question of where pharmacotherapy sits alongside airway treatment in obesity-related sleep apnea.
Here is what this week's evidence adds up to in Endocrinology. First, incretin-based therapy now has randomized phase 3 evidence of large apnea reductions with retatrutide, though the drug is investigational and responses were smaller in diabetes. Second, observational data suggest incretin choice and use may matter in groups trials rarely include, with semaglutide associated with lower mortality than dulaglutide in haemodialysis and incretins underused in normal-weight fatty liver disease; both findings need confirmation. Third, in adults over 75, SGLT2 inhibitors showed no signal of excess harm compared with DPP-4 inhibitors, but estimates for ketoacidosis, falls and fractures remain imprecise. Fourth, in cystic fibrosis-related diabetes, mortality rises with HbA1c starting at modest levels, an association rather than proof that tighter control helps. Finally, long-acting hormone replacements show durable or comparable efficacy in hypoparathyroidism and Turner syndrome, while treatment thresholds for mild thyroid dysfunction in pregnancy remain genuinely contested.
That's your roundup for This Week in Endocrinology. The full transcript and references are available on the episode page. This is an AI-curated summary — for clinical decisions, always consult primary sources and current guidelines. See you next week.
If this weekly briefing is useful, follow the show in your podcast app so new episodes arrive automatically. And if it saves you time, a quick rating in your podcast app helps other physicians find the show.
This is an automated summary generated by artificial intelligence, which can make mistakes. Always review the original source materials.
Spot something worth flagging?
Get this every week in your podcast app — free.
New endocrine episodes land in your feed automatically — listen on your commute.