Daily Endocrinology Research Analysis
Analyzed 90 papers and selected 3 impactful papers.
Summary
Across endocrinology, three studies stood out: a double-blind RCT showed that adding phentermine-topiramate to a digitally enhanced lifestyle program produced large, sustained weight loss and reduced estimated ASCVD risk. A nationwide French cohort linked gestational diabetes to early and long-term excess risk of kidney disease. A population-scale analysis revealed distinct acne incidence patterns after gender-affirming hormones, especially a sharp rise in the first year of testosterone in transmasculine individuals.
Research Themes
- Adjunct pharmacotherapy with digital lifestyle intervention for obesity
- Endocrine therapy–associated dermatologic outcomes in transgender care
- Pregnancy-related dysglycemia and long-term renal risk
Selected Articles
1. Addition of Phentermine-Topiramate to a Digitally Enhanced Lifestyle Intervention: A Double-Blind Randomized Clinical Trial.
In a 12-month, double-blind RCT (n=80), adding phentermine-topiramate ER to a digitally enhanced lifestyle program yielded markedly greater weight loss than placebo at 3 and 12 months and reduced estimated ASCVD risk. The trial supports combining pharmacotherapy with digital behavioral support to achieve durable weight loss.
Impact: Demonstrates robust, sustained weight loss and cardiometabolic risk improvement with an adjunct therapy that can be deployed alongside scalable digital interventions.
Clinical Implications: Consider phentermine-topiramate ER as an adjunct to structured digital lifestyle programs for adults with obesity to enhance and sustain weight loss while improving ASCVD risk estimates; monitor for medication tolerability and long-term adherence.
Key Findings
- At 3 months, mean weight loss was 10.82 kg vs 4.04 kg (difference −6.78 kg; p=0.002).
- At 12 months, mean weight loss was 15.32 kg vs 5.85 kg (difference −9.48 kg; p<0.001).
- Estimated ASCVD risk decreased by 3.35% from baseline with phentermine-topiramate (p=0.004).
Methodological Strengths
- Randomized, double-blind, placebo-controlled design with 12-month follow-up
- Prospective trial registration (ClinicalTrials.gov NCT04408586)
Limitations
- Single-center study with relatively small sample size (n=80)
- Limited reporting of adverse events and generalizability to diverse settings
Future Directions: Conduct multicenter, larger RCTs evaluating long-term safety, maintenance of weight loss beyond 12 months, and comparative effectiveness against other anti-obesity agents within digitally supported care pathways.
OBJECTIVE: This study compared the effects of phentermine-topiramate-ER (mid-dose 7.5/46 mg) versus placebo on weight loss and cardiovascular disease (CVD) risk outcomes when used as an adjunct to a digitally enhanced lifestyle intervention (DELI). METHODS: We conducted a 12-month, randomized, double-blind, placebo-controlled trial at a single tertiary academic center in the United States (June 2020-June 2022). Eighty participants with obesity (BMI ≥ 30 kg/m RESULTS: At 3 months, the phentermine-topiramate group lost a mean of 10.82 kg versus 4.04 kg in the placebo group (mean difference -6.78 kg; p = 0.002). At 12 months, weight loss was 15.32 kg versus 5.85 kg, respectively (mean difference -9.48 kg; p < 0.001). Participants receiving phentermine-topiramate-ER experienced a 3.35% reduction in the estimated atherosclerotic CVD risk compared to baseline (p = 0.004). CONCLUSIONS: Phentermine-topiramate-ER, when combined with a DELI, produced significant and sustained weight loss and reduced CVD risk in adults with obesity. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04408586.
2. Acne Incidence and Severity in Transgender Individuals.
In a matched cohort of 280,997 individuals, acne incidence was substantially higher among transmasculine individuals, especially in the first year after testosterone initiation (HR 8.29 vs cisgender men), and remained elevated thereafter. Transfeminine individuals also experienced higher acne risk than cisgender men after estradiol initiation, though lower than cisgender women; moderate-to-severe acne patterns paralleled these findings.
Impact: Provides population-level risk estimates to guide anticipatory counseling and early dermatologic management during gender-affirming hormone therapy.
Clinical Implications: Initiate proactive acne surveillance and guideline-concordant therapy when starting testosterone in transmasculine individuals, with heightened attention during the first year; counsel transfeminine patients that acne may arise after estradiol and plan timely management.
Key Findings
- Five-year cumulative acne incidence: transmasculine 15.8% vs matched cis men 3.8% and cis women 10.5%.
- Highest acne risk in transmasculine individuals during first year after testosterone (HR 8.29 vs cis men; HR 2.63 vs cis women) with persistent elevation thereafter.
- Transfeminine acne risk increased after estradiol vs cis men (HR 1.56) but remained lower than cis women (HR 0.53); moderate-to-severe acne showed similar patterns.
Methodological Strengths
- Very large, multicenter matched cohort with up to 5 years of follow-up
- Rigorous comparative analyses by transgender status and hormone initiation timing
Limitations
- Observational design with potential residual confounding and reliance on coded EHR diagnoses
- Care patterns within integrated health systems may limit generalizability to other settings
Future Directions: Prospective studies to evaluate preventive regimens at hormone initiation and to optimize acne management algorithms tailored to transgender populations.
IMPORTANCE: Acne commonly affects transgender individuals prescribed gender-affirming hormone therapy, yet population-level incidence data remain limited. OBJECTIVE: To compare the incidence of acne and moderate to severe acne in transgender individuals, including those initiating gender-affirming hormone therapy, with matched cisgender individuals. DESIGN, SETTING, AND PARTICIPANTS: A retrospective matched cohort study of electronic health record data was carried out across 4 Kaiser Permanente health plan regions. Index dates were the earliest documentation of transgender status, ranging from January 2006 to February 2022, with up to 5 years of follow-up. Participants included individuals without baseline acne, transmasculine individuals, and transfeminine individuals matched with cisgender male and female individuals. Analyses were conducted from November 2024 to November 2025. MAIN OUTCOMES AND MEASURES: The primary outcome was incident acne (first acne-coded visit after the index date). The secondary outcome was moderate to severe acne (incident acne followed by prescription fill for isotretinoin or 30 or more days of oral antibiotics). Exploratory analyses compared acne care utilization by transgender status. RESULTS: Overall, 280 997 individuals without baseline acne, including 11 234 transmasculine and 9486 transfeminine individuals, were matched to 132 462 cisgender men and 127 815 cisgender women on age, self-reported race and ethnicity (25 340 Asian [9.0%]; 23 234 non-Hispanic Black [8.3%]; 56 876 Hispanic [20.2%]; 153 666 non-Hispanic White [54.7%]; 6989 other [2.5%]), enrollment year, and region. Of these, 12 156 transgender individuals initiated gender-affirming hormone therapy after the index date. The mean (SD) age at index date was 27.7 (10.0) years for transmasculine individuals and 33.2 (13.5) years for transfeminine individuals. Cumulative incidence of acne at 5 years was 15.8% in transmasculine individuals, 3.8% in matched cisgender male individuals, and 10.5% in matched cisgender female individuals and was 6.0% in transfeminine individuals, 2.9% in matched cisgender men, and 8.4% in matched cisgender women. Acne risk in transmasculine individuals was highest in the first year after testosterone initiation (vs matched cisgender male individuals: hazard ratio (HR), 8.29; 95% CI, 7.11-9.68; vs matched cisgender female individuals: HR, 2.63; 95% CI, 2.33-2.97) and remained higher in subsequent years than among cisgender men (HR, 5.29; 95% CI, 4.45-6.28) and cisgender women (HR, 1.69; 95% CI, 1.46-1.96). Acne risk was higher in transfeminine individuals after starting estradiol than cisgender men (HR, 1.56; 95% CI, 1.31-1.84) and lower than cisgender women (HR, 0.53; 95% CI, 0.46-0.62). Moderate to severe acne incidence followed similar patterns. CONCLUSIONS AND RELEVANCE: This study revealed distinct acne incidence patterns in transgender individuals compared with matched cis male and female cohorts. Clinicians should monitor and treat acne in transmasculine individuals prescribed testosterone per clinical guidelines, particularly during the first year. Clinicians should also recognize that acne may develop in transfeminine individuals after estradiol initiation.
3. Gestational Diabetes Mellitus and Incident Kidney Disease: A Nationwide French Cohort Study.
In 1.44 million parous women, prior GDM was associated with higher risks of CKD (aHR 1.46) and AKI (aHR 1.18) over 10 years. Risks appeared as early as 1-year postpartum, attenuated after accounting for incident hypertension and type 2 diabetes, and were greater with recurrent GDM.
Impact: Defines kidney risk trajectories after GDM at national scale, highlighting early postpartum vulnerability and the incremental risk with recurrent GDM episodes.
Clinical Implications: Implement postpartum renal risk stratification and follow-up in women with prior GDM, with earlier monitoring for those with recurrent GDM; integrate blood pressure and diabetes prevention/control to mitigate CKD progression.
Key Findings
- Prior GDM associated with higher CKD risk (aHR 1.46, 95% CI 1.36–1.55) and AKI risk (aHR 1.18, 95% CI 1.11–1.25).
- Effect sizes attenuated after accounting for incident postpartum hypertension and type 2 diabetes (CKD aHR 1.10; AKI aHR 1.01).
- Elevated kidney risk evident by 1-year postpartum and greater with two or more GDM episodes versus one.
Methodological Strengths
- Nationwide, population-based cohort with very large sample size and 10-year follow-up
- Time-to-event modeling (Cox regression) with analyses of timing and recurrence
Limitations
- Outcomes based on hospitalization codes may miss outpatient or subclinical kidney disease
- Residual confounding and limited clinical detail inherent to administrative datasets
Future Directions: Evaluate targeted postpartum renal screening pathways after GDM and test interventions reducing CKD risk, especially in women with recurrent GDM, in pragmatic trials.
BACKGROUND: The extent to which gestational diabetes mellitus (GDM) influences the risk of kidney disease remains unknown. We investigated the associations between GDM and incidence of kidney disease, including CKD and AKI. METHODS: This nationwide population-based cohort study included 1,441,317 parous women in France during 2012-2013. We used Cox regression to investigate the: 1) association of GDM with incident hospitalization for AKI or CKD, 2) timing to postpartum GDM-related kidney disease, and 3) GDM recurrence and the incidence of kidney disease. RESULTS: Over a 10-year period, women with a history of GDM (n=103,122 [7.2%]) had a 46% higher risk of CKD (aHR: 1.46, 95% CI: 1.36, 1.55) and a 18% higher risk of AKI (aHR: 1.18, 95% CI: 1.11, 1.25), compared to those without a history of GDM. Accounting for post-partum incident hypertension and type 2 diabetes attenuated effect estimates - 10% for CKD (aHR: 1.10. 95% CI: 1.02, 1.19) and 1% for AKI (aHR: 1.01, 95% CI: 0.95, 1.08). The elevated risk of kidney disease was apparent at one-year post-partum and more pronounced among women with two or more GDM episodes than among those with one GDM episode. CONCLUSIONS: GDM was mainly associated with an increased risk of CKD; which is present early in the post-partum and higher among women with repeated GDM.