Triple diabetes pill lowered blood sugar and weight in six-month single-centre study

A fixed-dose combination pill containing sitagliptin, dapagliflozin and metformin was associated with substantial improvements in blood sugar control among patients with type 2 diabetes who had not reached their glycaemic targets on prior treatment, according to a prospective observational study published in Discover Pharmaceutical Sciences. Over six months of follow-up, average HbA1c — a measure of long-term blood sugar control — fell from 10.1 percent to 6.6 percent, fasting blood sugar dropped from 160.1 mg/dL to 103.3 mg/dL, and post-prandial blood sugar, measured after meals, declined from 282 mg/dL to 161.6 mg/dL. All three changes were statistically significant, with P values below 0.0001.

The cohort had a mean age of 58.5 years, with a standard deviation of 11.4 years, and 58.3 percent of participants were male. Most patients were older than 45, and nearly half were above 60. The mean duration of diabetes was 6.8 years.

The population was characterised by a heavy burden of comorbidities. Every participant had hypertension, and 98.5 percent had dyslipidaemia. All individuals in the study had a body mass index above 25 kg/m². The authors note that this high prevalence of hypertension and dyslipidaemia may reflect the tertiary care setting, where patients commonly present with multiple coexisting conditions. Because patients were already on the combination therapy before being recruited, the researchers acknowledge that the design may have introduced selection bias, since individuals who could not tolerate the treatment and stopped taking it earlier would not have been captured.

The study’s authors argue that combining agents with complementary modes of action can enhance therapeutic efficacy while reducing pill burden, which in turn may improve patient compliance. They also note that the lack of pharmacokinetic interactions between the three drugs supports their combined use, and that the metformin dose used was lower than guideline recommendations, possibly reflecting tolerability or routine prescribing patterns.

Improvements in glycaemic parameters emerged early and were sustained. At three months, mean HbA1c had dropped from 10.1 percent to 7.9 percent, and by six months it had reached 6.6 percent. Fasting blood sugar fell from 160.1 mg/dL at baseline to 103.1 mg/dL at three months and 103.3 mg/dL at six months, while post-prandial blood sugar declined from 282 mg/dL to 170 mg/dL at three months and 161.6 mg/dL at six months. At the six-month mark, the average reductions were 3.5 percent for HbA1c, 56.8 mg/dL for fasting blood sugar and 120.4 mg/dL for post-prandial blood sugar. The authors report that these improvements were consistent across subgroups defined by age, gender and duration of diabetes, including patients with long-standing disease of more than five years.

Target attainment varied considerably by parameter. Approximately 80 percent of patients achieved an HbA1c below 7 percent at six months, up from 15.1 percent at three months. However, target fasting blood sugar below 100 mg/dL was reached by only 41.3 percent of patients, and target post-prandial levels were achieved in just 21 percent. This pattern suggests that while the combination was effective at lowering average blood sugar over months, a substantial share of patients still did not reach the stricter targets for individual glucose measurements, particularly after meals.

Body weight also declined during the study, with a mean reduction of 5.9 kg over the six-month period. The authors suggest that the dapagliflozin component may contribute to weight loss through increased urinary glucose excretion, an effect reported in previous research. However, they caution that lifestyle advice was provided to participants but adherence to that advice was not systematically assessed, meaning the weight reduction cannot be attributed solely to the pharmacological effects of the drugs. The authors also note that the short follow-up and single-centre design mean that long-term outcomes such as sustained weight changes and cardiovascular effects could not be evaluated.

Safety findings were broadly reassuring within the limits of the study. The incidence of genitourinary tract infections remained similar during follow-up, at 2.4 percent versus 3.5 percent, a difference that was not statistically significant, and no treatment discontinuations due to adverse events were reported. They also point out that other class-related adverse effects were not specifically evaluated: SGLT2 inhibitors may be associated with volume depletion, DPP-4 inhibitors have been rarely linked to pancreatitis, and metformin is commonly associated with gastrointestinal disturbances and vitamin B12 deficiency.

Medication adherence was high throughout the study. Using the Hill-Bone Medication Adherence Scale, a self-reported instrument, the researchers found that good compliance, defined as 80 to 100 percent, was reported by 95.2 percent of patients at three months and 98 percent at six months. The authors acknowledge that because adherence was measured with a self-reported scale, reporting bias cannot be excluded, and they note that the Hill-Bone scale was originally developed for hypertension, so its use in diabetes may have inherent limitations.

The authors place their findings in the context of earlier trials of the same triple combination, which reported mean HbA1c reductions of 1.45 to 1.73 percent, generally superior to dual therapy and without an increase in hypoglycaemia. The present study adds real-world evidence from a single Indian centre, along with data on adherence and patient education that prior research has largely not addressed. Nevertheless, the authors are explicit about the constraints of their work: the sample size was relatively small, the study was conducted at a single centre over only six months, there was no comparator group, and the statistical analysis relied on pairwise comparisons rather than repeated-measures methods. In the absence of a control group, the observed improvements cannot be attributed solely to the intervention. The authors conclude that the triple fixed-dose combination was associated with improved glycaemic control and good tolerability in this population, but they emphasise that confirmation in larger, well-designed comparative studies with longer follow-up is warranted.

Subject of Research: Glycaemic efficacy, safety and medication adherence of a triple fixed-dose combination of sitagliptin, dapagliflozin and metformin in type 2 diabetes

Article Title: Safety efficacy and treatment compliance of triple fixed dose combination dapagliflozin sitagliptin and metformin in patients with type 2 diabetes mellitus

Article References: Monica L, A. M., & Patricia L, A. M. (2026). Safety efficacy and treatment compliance of triple fixed dose combination dapagliflozin sitagliptin and metformin in patients with type 2 diabetes mellitus. Discover Pharmaceutical Sciences, 2(1), Article 13. https://doi.org/10.1007/s44395-026-00049-1

Image Credits: AI Generated

DOI: 10.1007/s44395-026-00049-1

Keywords: type 2 diabetes, fixed-dose combination, dapagliflozin, sitagliptin, metformin, HbA1c, glycaemic control, medication adherence, observational study, weight reduction, genitourinary infections, India