Daily Endocrinology Research Analysis
A living network meta-analysis and an accompanying living clinical practice guideline from BMJ synthesize evidence from 869 randomized trials on type 2 diabetes medications, offering risk‑stratified recommendations and clear quantification of benefits and harms. Complementing these practice-facing resources, a prospective cohort study in The Lancet Diabetes & Endocrinology shows that recovery of β-cell function is the dominant driver of prediabetes remission.
Summary
A living network meta-analysis and an accompanying living clinical practice guideline from BMJ synthesize evidence from 869 randomized trials on type 2 diabetes medications, offering risk‑stratified recommendations and clear quantification of benefits and harms. Complementing these practice-facing resources, a prospective cohort study in The Lancet Diabetes & Endocrinology shows that recovery of β-cell function is the dominant driver of prediabetes remission.
Research Themes
- Risk-stratified pharmacotherapy for type 2 diabetes
- Living evidence synthesis and guideline development
- β-cell function as a determinant of dysglycemia remission
Selected Articles
1. Medications for adults with type 2 diabetes: a living systematic review and network meta-analysis.
This living network meta-analysis synthesized 869 randomized trials (n=493,168) across 13 drug classes, confirming cardiovascular and kidney benefits of SGLT-2 inhibitors, GLP-1RAs, and finerenone (in CKD), and identifying tirzepatide as the most effective agent for weight loss. It also quantified drug-specific harms (e.g., genital infections and ketoacidosis with SGLT-2 inhibitors; severe GI events with tirzepatide; hyperkalaemia with finerenone) and provided risk‑stratified absolute effects via an interactive tool.
Impact: This is the most comprehensive, continuously updated comparison of modern type 2 diabetes therapies, directly informing individualized treatment by quantifying absolute benefits and harms across baseline risk strata.
Clinical Implications: Supports prioritizing SGLT-2 inhibitors and GLP-1RAs (and finerenone in CKD) for cardio-renal protection, and tirzepatide for substantial weight loss, while guiding monitoring for class-specific harms (e.g., genital infections, ketoacidosis, hyperkalaemia). Enables risk‑stratified, patient‑centered choices.
Key Findings
- Included 869 randomized trials with 493,168 participants across 13 drug classes and 26 outcomes.
- SGLT-2 inhibitors, GLP-1RAs, and finerenone (in CKD) reduce cardiovascular and kidney events (moderate-to-high certainty).
- Tirzepatide produced the largest mean weight loss (MD −8.63 kg; 95% CI −9.34 to −7.93).
- Harms: SGLT-2 inhibitors increased genital infections (OR 3.29) and ketoacidosis (OR 2.08); finerenone increased severe hyperkalaemia (OR 5.92); tirzepatide increased severe GI events (OR 4.21).
- Absolute effects vary by baseline risk; interactive tool provides risk-stratified comparisons.
Methodological Strengths
- Living, PRISMA-aligned systematic review with frequentist NMA and GRADE certainty ratings
- Large evidence base (869 RCTs) with registered protocol (PROSPERO) and interactive absolute-effect tool
Limitations
- Heterogeneity across trials and low to very low certainty for several microvascular/neurocognitive outcomes
- Network meta-analysis assumptions and trial populations may limit generalizability to all care settings
Future Directions: Expand living updates to include emerging agents and head-to-head comparative effectiveness on patient-important outcomes; refine risk calculators with real-world data.
2. Cardiovascular, kidney related, and weight loss effects of therapeutics for type 2 diabetes: a living clinical practice guideline.
This living guideline issues risk‑stratified recommendations for SGLT‑2 inhibitors, GLP‑1 receptor agonists, finerenone, and tirzepatide, balancing benefits, harms, and patient burdens using GRADE. It strongly recommends SGLT‑2 inhibitors or GLP‑1RAs for higher‑risk patients (established CVD/CKD/HF), offers weak support in moderate risk, advises against early use at low risk, and weakly favors tirzepatide in adults with obesity.
Impact: Provides globally relevant, GRADE-based, living guidance directly linked to a companion living NMA, enabling individualized, risk‑stratified diabetes pharmacotherapy.
Clinical Implications: Clinicians can tailor therapy by baseline CVD/CKD/HF risk and obesity, prioritizing SGLT‑2 inhibitors/GLP‑1RAs in higher‑risk patients, considering finerenone in CKD with higher risk, and reserving these agents at low risk; shared decision‑making incorporates values, accessibility, and harms.
Key Findings
- Issues risk-stratified recommendations for SGLT-2 inhibitors, GLP-1RAs, finerenone, and tirzepatide based on GRADE.
- Strong recommendation for SGLT-2 inhibitors or GLP-1RAs in higher-risk adults (established CVD/CKD/HF).
- Weak recommendation against early use in lower-risk adults; weak in favour at moderate risk; finerenone favoured weakly only in CKD at higher risk.
- Weak recommendation in favour of tirzepatide in adults with obesity across risk strata.
- Linked to a living SR/NMA updated to July 31, 2024; international panel including patient partners.
Methodological Strengths
- Trustworthy guideline standards with GRADE and explicit patient-centered trade-offs
- Linked to a living systematic review/network meta-analysis and risk prediction/value-preference reviews
Limitations
- Recommendations depend on evolving evidence and may change with new data
- Implementation may vary by access, costs, and health system contexts
Future Directions: Update recommendations as new head-to-head trials and agents emerge; integrate real-world evidence and cost‑effectiveness into risk‑stratified guidance.
3. The central role of recovery of β-cell function in the remission of prediabetes: a prospective cohort study in Canada.
In 182 postpartum women with prediabetes, remission was most strongly predicted by improvements in β-cell function (change in ISSI-2; aOR 3.80), followed by insulin sensitivity (change in Matsuda index; aOR 2.28), after adjustment for clinical risk factors. Baseline and follow-up indices consistently favored higher β-cell function in those achieving remission.
Impact: Clarifies a long-debated mechanism by demonstrating that β-cell recovery, more than insulin sensitivity alone, drives remission of prediabetes, informing targets for intervention.
Clinical Implications: Interventions to induce remission should prioritize strategies that restore β-cell function (e.g., weight loss interventions that improve β-cell responsiveness, timely pharmacotherapy), in addition to improving insulin sensitivity.
Key Findings
- Among 182 postpartum women with prediabetes, 100 achieved remission by the second visit (median 13.0 months postpartum).
- Remission was associated with larger improvements in β-cell function (ISSI-2; aOR 3.80) and insulin sensitivity (Matsuda index; aOR 2.28).
- Baseline and follow-up ISSI-2 and IGI/FPI were higher in remission vs non-remission groups.
- Change in ISSI-2 was the top predictor of remission (largest change in model deviance).
Methodological Strengths
- Prospective design with serial OGTT and validated indices (ISSI-2, Matsuda, HOMA-IR, IGI/FPI)
- Adjusted logistic regression accounting for key diabetes risk factors
Limitations
- Population limited to postpartum women; generalizability to broader prediabetes populations may be limited
- Observational design cannot prove causality; modest sample size
Future Directions: Test interventions that specifically enhance β-cell function for inducing durable remission; validate findings in diverse, non-postpartum prediabetes cohorts.