Table 2.
An overview of the reported preventive measures and incidence rates of DKA and severe hypoglycaemia over a 12-month period.
| Trial | Adjunct drug and route | Preventive measures | Doses | DKA (%) | Severe Hypoglycaemia (%) |
|---|---|---|---|---|---|
| DEPICT-1 [114], DEPICT-2 [115] | Dapagliflozin; oral once daily |
- Blood glucose monitoring, min. 4 times/ day, and 6 times/day for specific intense phase. - Home blood ketone measurement. - Diet and exercise counselling. - Instructions on DKA risk. - Insulin dose adjustment (not >20%) throughout study. |
5 mg | 4.0; 4.1 | 10.5; 8.9 |
| 10 mg | 3.4; 3.7 | 8.4; 9.6 | |||
| Placebo | 1.9; 0.4 | 11.5; 8.5 | |||
| inTandem1 [78]; inTandem2 [79] | Sotagliflozin; oral once daily |
- Prompt and systematic address of ketosis, - Instructions on DKA risk, symptoms, management - Blood/urine ketone measurement, insulin dose adjustment |
200 mg | 3.4; 2,3 | 6.5; 5.0 |
| 400 mg | 4.2; 3.4 | 6.5; 2.3 | |||
| Placebo | 0.4; 0 | 9.7; 5.0 | |||
| Phase III study [116] | Ipragliflozin; oral once daily |
- Blood glucose monitoring – 7 times/day for specific intense phase - Insulin and adjunct ipragliflozin dose adjustment throughout study |
50 mg & 100 mg | 0 | 0 |
| ADJUNCT-ONE [74] | Liraglutide; subcutaneously once daily |
- Begin with a low dose - Gradually titrate up - Insulin dose adjustment (~25% on randomisation day, ~10% on dose escalation) |
0.6 mg | 0.9 | 9.1 |
| 1.2 mg | 0.3 | 6.3 | |||
| 1.8 mg | 0.8 | 8.1 | |||
| Placebo | 0 | 10.9 | |||
| Real-world study | Adjunct drug | Preventive measures | Doses | DKA (%) | Severe Hypoglycaemia (%) |
| Palanca et al. [97] |
a. Empagliflozin b. Dapagliflozin c. Canagliflozin |
- Instructions on DKA risk, symptoms, management - Home blood/ urine ketone measurement - Card describing the STICH protocol |
a. 5 mg, b. 5 mg, c. 50 mg |
2.6 | 0 |
|
a. 10, 12.5, and 25 mg b. 10 mg c. 100 mg |
4.1 | 0 | |||
| Seufert et al, 2021 [98] |
a. Dapagliflozin, b. Empagliflozin |
- Highly stringent patient selection - Intense surveillance over the treatment course |
a. 5 to 10 mg b. 10 to 25 mg |
0 | 3.0 |
| Edwards et al, 2023 [76] | Liraglutide, semaglutide, dulaglutide, exenatide, albiglutide | - Preferentially choice for patients at risk of DKA | Not reported | 3.9 | 1.3 |
| Empagliflozin, dapagliflozin, canagliflozin | - Not reported | Not reported | 12.8 | 2.6 | |
| Al-Ozairi et al, 2023 [77] | Dapagliflozin |
- Enroled in a structured education program - Home blood/ urine ketone measurement, CGM for > 2 months - Emphasis on sick day rules |
Not reported | 1.1 | 0 |
| Liraglutide | 1.2 | 1.2 | |||
| Combination | 0 | 0 |