Pioglitazone reduces serum ketone bodies in sodium‐glucose cotransporter ‐2 inhibitor‐treated non‐obese type 2 diabetes: A single‐centre, randomized, crossover trial
Authors' conclusion
Supplementation of pioglitazone could alleviate canagliflozin-induced ketone bodies. This benefit may be closely associated with decreased substrate NEFAs rather than other factors including glucagon, fasting insulin and NA.
Study context
- Population
- Non-obese patients with T2D treated with the SGLT2i canagliflozin; mean age 49 ± 7.97 years, BMI 25.35 ± 2.22 kg/m²1 discontinued in washout
- Participants
- 25 patients
- Comparison
- Pioglitazone plus canagliflozin vs canagliflozin monotherapy
- Primary endpoint
- Change (Δ) in β-hydroxybutyric acid (β-HBA) before and after treatment
- Follow-up
- 4 weeks per treatment period
Methodological detailssingle-centre, two periods of 4 weeks, 4-week washout, randomized 1:1
- Single-centre
- Two periods of 4 weeks
- 4-week washout
- Randomized 1:1
Primary result
As reported in the abstract
Δβ-HBA
PIOG + CANA
219.84
± 80.21 · μmol/L
CANA
317.69
± 83.07 · μmol/L
P < 0.001
Secondary outcomes
| Outcome | PIOG + CANA | CANA | P value |
|---|---|---|---|
| ΔacetoneSignificantly smaller with PIOG + CANA | 8.98 ± 4.17 μmol/L | 12.29 ± 5.27 μmol/L | P = 0.018 |
Δacetoacetate
- Difference between groups not significant for acetoacetate
Rate of conversion into urinary ketones
- Elevated after both interventions
NEFA, glucagon, glucagon to insulin ratio and noradrenaline
- Significantly increased after both CANA and PIOG + CANA; only non-esterified fatty acids (NEFAs) differed significantly between groups
Correlation of ΔNEFA with Δketones
- Difference in ΔNEFA significantly associated with differences in Δβ-HBA and Δacetoacetate
Original publication
Pioglitazone reduces serum ketone bodies in sodium‐glucose cotransporter ‐2 inhibitor‐treated non‐obese type 2 diabetes: A single‐centre, randomized, crossover trial. Diabetes Obes Metab. Published 3 May 2024. doi:10.
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