Daily Endocrinology Research Analysis
A double-blind multicenter RCT showed that adding dapagliflozin to calorie restriction significantly increased type 2 diabetes remission versus calorie restriction alone. A national target trial emulation found no overall excess thyroid cancer risk with GLP-1RAs vs comparators, but a higher risk of diagnoses in the first year, likely reflecting enhanced detection. A nationwide real-world cohort showed diabetes remission associates with ~30% lower cardiovascular disease risk, even without weight
Summary
A double-blind multicenter RCT showed that adding dapagliflozin to calorie restriction significantly increased type 2 diabetes remission versus calorie restriction alone. A national target trial emulation found no overall excess thyroid cancer risk with GLP-1RAs vs comparators, but a higher risk of diagnoses in the first year, likely reflecting enhanced detection. A nationwide real-world cohort showed diabetes remission associates with ~30% lower cardiovascular disease risk, even without weight loss.
Research Themes
- Type 2 diabetes remission strategies (SGLT2 inhibitor plus diet)
- Medication safety signal evaluation (GLP-1RA and thyroid cancer)
- Cardiometabolic outcomes linked to diabetes remission in real-world care
Selected Articles
1. Dapagliflozin plus calorie restriction for remission of type 2 diabetes: multicentre, double blind, randomised, placebo controlled trial.
In 328 adults with type 2 diabetes, dapagliflozin plus calorie restriction produced a 44% remission rate at 12 months versus 28% with calorie restriction alone, alongside greater reductions in weight and HOMA-IR and improved metabolic risk factors. Adverse events were similar between groups.
Impact: This high-quality RCT demonstrates a practical, pharmacologically-augmented dietary strategy to achieve diabetes remission, a central goal in modern diabetes care.
Clinical Implications: Consider SGLT2 inhibitor plus structured calorie restriction for remission-oriented care in overweight/obese patients with early T2D, with close monitoring and individualized dosing.
Key Findings
- Diabetes remission at 12 months: 44% with dapagliflozin plus calorie restriction vs 28% with calorie restriction alone (RR 1.56, 95% CI 1.17–2.09).
- Greater reductions in body weight (−1.3 kg vs placebo) and HOMA-IR (difference −0.8) with dapagliflozin.
- Improved body fat, systolic blood pressure, and metabolic risk factors without increased adverse events.
Methodological Strengths
- Multicenter, double-blind, randomized, placebo-controlled design
- Predefined remission endpoint with clinically meaningful composite criteria
Limitations
- Conducted in China; generalizability to other populations requires validation
- 12-month duration limits assessment of durability of remission
Future Directions: Longer-term and multinational trials assessing durability, cost-effectiveness, micro/macrovascular outcomes, and optimal patient selection for remission protocols.
2. GLP-1RA Use and Thyroid Cancer Risk.
In a target trial emulation of 351,913 adults with type 2 diabetes, GLP-1RA initiation was not associated with an overall increased thyroid cancer risk versus SGLT2i, DPP4i, or sulfonylureas, but showed a higher risk within the first year (HR 1.85), likely reflecting detection bias. Absolute risks were low across groups.
Impact: Addresses a timely safety concern amid widespread GLP-1RA use, with large-scale real-world data and causal emulation methods.
Clinical Implications: Clinicians should contextualize the low absolute risk and consider potential early detection effects; routine vigilance and appropriate thyroid evaluation may be reasonable during the first year without over-screening.
Key Findings
- Overall thyroid cancer risk with GLP-1RA vs comparators was not significantly increased (HR 1.24; 95% CI 0.88–1.76).
- Within the first year after initiation, thyroid cancer diagnoses were higher (HR 1.85; 95% CI 1.11–3.08), amplified in as-treated analysis (HR 2.07).
- Absolute incidence was low across all drug classes (0.17%–0.23%).
Methodological Strengths
- Target trial emulation with inverse propensity score weighting and piecewise hazards
- Very large, national, multi-payer claims dataset with mITT and as-treated analyses
Limitations
- Observational design subject to residual confounding and detection bias
- Cancer subtype, nodule workup intensity, and imaging surveillance details limited in claims
Future Directions: Linkage studies with cancer registries and imaging/laboratory data to parse detection vs causation; mechanistic and pharmacoepidemiologic studies by GLP-1RA class and dose.
3. Impact of diabetes remission or progression on the incidence of cardiovascular disease in Japan: historical cohort study using a nationwide claims database.
In a nationwide Japanese cohort (n=299,967; median follow-up 5 years), diabetes remission was associated with a ~30% lower CVD risk versus continued diabetes (HR 0.71), independent of BMI change. Individuals with diabetes progression had substantially higher CVD rates.
Impact: Provides real-world evidence that achieving diabetes remission translates into reduced cardiovascular events independent of weight loss, reinforcing remission as a meaningful clinical target.
Clinical Implications: Remission-focused care may lower CVD risk even without weight loss; prioritize strategies (e.g., dietary, pharmacologic, combination) to achieve and sustain remission, and intensify CVD risk management in non-remitters and progressors.
Key Findings
- Compared to DM+/no remission, DM+/remission had lower CVD risk (HR 0.71, 95% CI 0.57–0.89).
- CVD incidence rates per 1000 person-years: 7.96 (DM+/no remission), 4.76 (DM+/remission), 1.99 (DM−/no progression), 5.47 (DM−/progression).
- Benefit of remission persisted regardless of BMI change (HR 0.75 with BMI ≤0% change; HR 0.66 with BMI >0% change).
Methodological Strengths
- Very large nationwide cohort with multivariable Cox modeling
- A priori classification of remission/progression using HbA1c and medication changes
Limitations
- Observational design; potential residual confounding and misclassification of remission status
- Claims-based data may lack granularity on lifestyle, imaging, and subclinical disease
Future Directions: Prospective validation assessing durability of remission and cause-specific CVD outcomes; evaluation of remission-inducing interventions and health-economic impact.