Triple Combination Therapy Effective for Drug-Naive Type 2 Diabetes Patients, shows new Study
Korea: A study has demonstrated that initiating treatment with a triple combination therapy (TCT) comprising metformin, dapagliflozin, and saxagliptin is both safe and effective for drug-naive patients diagnosed with type 2 diabetes (T2D) when compared to stepwise add-on therapy (SAT).
"Compared to SAT, initial TCT effectively lowered HbA1c levels with higher tolerability and safety for 104 weeks among newly diagnosed patients with T2D," the researchers reported. The findings from the TRIPLE-AXEL study, published in Diabetes, Obesity and Metabolism, suggest a novel strategy for initial combination therapy in type 2 diabetes patients.
Nam Hoon Kim, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea, and colleagues aimed to evaluate the tolerability and efficacy of an initial triple combination therapy compared with conventional stepwise add-on therapy in patients with newly diagnosed type 2 diabetes.
For this purpose, the research team conducted a multicentre, randomized, 104-week, open-label trial comprising 105 patients with drug-naïve T2D (with HbA1c level ≥ 8.0%, < 11.0%). They were randomized to the TCT (1000 mg of metformin, 10 mg of dapagliflozin, and 5 mg of saxagliptin once daily) or SAT (initiated with metformin, followed by glimepiride and sitagliptin) groups.
The primary measure of success was the percentage of patients achieving an HbA1c level below 6.5% without experiencing hypoglycemia, gaining 5% or more in weight, or needing to stop medications due to adverse events by the 104-week mark.
The study led to the following findings:
- HbA1c reduction from baseline at week 104 was similar between the groups (the least squares mean change was −2.56% in the TCT group vs. –2.75% in the SAT group).
- The primary outcome was achieved in 39.0% and 17.1% of the TCT and SAT groups, respectively, with a risk difference of 22.0.
- HbA1c level less than 6.5% at week 104 was 46.3% in both the TCT and SAT groups, whereas the incidence of hypoglycemia, weight gain, or discontinuation of drugs was 16.7% and 62.0% in the TCT and SAT groups, respectively.
- TCT was well-tolerated and had fewer adverse events than SAT.
In conclusion, although each drug's glycemic efficacy in the triple combination therapy was modest, the drug combination led to a 2-year durable glycemic efficacy, with greater than a 2.5% reduction in A1c levels from baseline. Overall, the study results suggest a novel strategy for initial combination therapy in newly diagnosed T2D patients.
In addition, the initial TCT was linked with an improvement in multiple cardiovascular risk factors compared with SAT.
Reference:
Kim NH, Moon JS, Lee YH, Cho HC, Kwak SH, Lim S, Moon MK, Kim DL, Kim TH, Ko E, Lee J, Kim SG. Efficacy and tolerability of initial triple combination therapy with metformin, dapagliflozin and saxagliptin compared with stepwise add-on therapy in drug-naïve patients with type 2 diabetes (TRIPLE-AXEL study): A multicentre, randomized, 104-week, open-label, active-controlled trial. Diabetes Obes Metab. 2024 Jun 10. doi: 10.1111/dom.15705. Epub ahead of print. PMID: 38853720.
