Association of dipeptidyl peptidase‐4 inhibitor initiation at glycated haemoglobin <7.5% with reduced major clinical events mediated by low glycated haemoglobin variability
Authors' conclusion
In Chinese patients with T2D, avoiding therapeutic inertia with intensified glycaemic control at HbA1c <7.5% using drugs with low risk of hypoglycaemia and good tolerability, such as DPP4i, delayed insulin treatment, reduced HbA1c variability and improved clinical events.
Study context
- Population
- Insulin-naïve patients with T2D initiating DPP-4i in Hong Kong, 2007–2019; 88.7% on metformin, 79.6% on sulphonylureas at baseline; 54.9% men; mean age 65.2 ± 11.4 yearsmatched cohort
- Participants
- 6,874 patients
- Exposure
- DPP-4i initiation at HbA1c <7.5% vs ≥7.5%
- Outcome
- Insulin initiation and clinical outcomes
- Follow-up
- Median 4.6 years
Methodological detailspropensity score-matched, territory-wide electronic medical records, Cox model with time-varying adjustment, mediation analysis
- Propensity score-matched
- Territory-wide electronic medical records
- Cox model with time-varying adjustment
- Mediation analysis
Main finding
As reported in the abstract
median follow-up 4.6 years
Hazard ratio (95% CI)
Low threshold + low HVSvs High threshold + high HVSinsulin initiation
0.35(0.31–0.40)
Low threshold + low HVSvs High threshold + high HVSMACE
0.76(0.66–0.88)
Low threshold + low HVSvs High threshold + high HVSHF
0.42(0.36–0.49)
Low threshold + low HVSvs High threshold + high HVSmortality
0.45(0.35–0.57)
- Between Low threshold + low HbA1c variability score (HVS) and High threshold + high HVS · end-stage kidney disease
- HR 0.65 (95% CI 0.36–0.49)
Observational data: associations, not effects.
Further findings
Mediation by reduced HbA1c variability
- Share of effect of DPP-4i initiation at HbA1c <7.5% vs ≥7.5% on outcomes explained by reduced HbA1c variability
- 31.1%-81.2%
Safety
| Outcome | HR (95% CI) | |
|---|---|---|
| Severe hypoglycaemia · median follow-up 4.6 years | 0.38 (0.34–0.44) | |
| 0.20.5125Hazard ratio (log scale) |
Original publication
Association of dipeptidyl peptidase‐4 inhibitor initiation at glycated haemoglobin <7.5% with reduced major clinical events mediated by low glycated haemoglobin variability. Diabetes Obes Metab. Published 27 May 2024. doi:10.
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