Multidrug combos provide optimal glycaemic control in T2D patients

A real-world study from India shows that multiple drug combinations effectively controlled blood sugar levels in individuals with type 2 diabetes (T2D).

“[In our study,] triple combinations showed optimal glycaemic control with the most significant HbA_1c reductions, while sodium glucose cotransporter-2 (SGLT2) inhibitor combinations provided additional cardiovascular benefits,” noted Dr Dhaval Patel from the Shreevin Sugar Care Diabetes Clinic, Himatnagar, Gujarat, India, at ATTD-Asia 2025.

Patel and colleagues conducted a retrospective analysis comprising 250 individuals with T2D (mean age 56.2 years, 64 percent men). Participants received fixed-dose combinations, the most frequent being dipeptidyl peptidase-4 (DPP-4) inhibitors plus metformin (n=90; 36 percent), followed by triple combinations with sulfonylureas (n=80; 32 percent) and SGLT2 inhibitors plus metformin (n=70; 28 percent). The follow-up period was 6 months. [ATTD-Asia 2025, abstract SOP030]

Overall, the mean HbA_1c decreased from 9.2 percent to 7 percent (p<0.001). The best glycaemic outcomes were achieved with triple combinations with sulfonylureas, yielding a mean HbA_1c reduction of 2.8 percent.

This aligns with robust evidence reflecting greater and more durable HbA_1c reduction with sulfonylurea-based combinations. [Diabetes Res Clin Pract 2016:116:149-158; Diabetes Care 2020;44:433-439; PeerJ 2015:3:e1461]

With combinations comprising SGLT2 inhibitors and metformin, the mean HbA_1c reduction was 2.2 percent, while for DPP-4 inhibitors plus metformin, the mean HbA_1c reduction was 1.7 percent.

In one study, SGLT2 inhibitors are favoured over DPP-4 inhibitors as add-on therapy to metformin when glycaemic targets have not been achieved, and in individuals who would benefit from the additional weight loss and cardiovascular disease benefits. [Diabetes Metab Res Rev 2018;34:e2981]

Other benefits

Patel also noted significant improvements in comorbidities. Approximately 80 percent of participants with hypertension achieved their blood pressure targets (<140/90), and 82 percent of patients with dyslipidaemia achieved their lipid goals.

These findings support evidence demonstrating the cardioprotective effect of antidiabetic agents. [Cardiovasc Endocrinol Metab 2019;8:96-105; Diabetes Care 2023;46:1300-1310]

Moreover, the pill burden dropped from a mean of 4.2 to 2.8 daily medications, representing a 33-percent reduction (p<0.001). “Fixed-dose combinations significantly reduced pill burden while improving patient outcomes across multiple comorbidities, supporting escalated combination therapy in poorly controlled diabetes,” Patel said.

Of note, SGLT2 inhibitor combinations led to weight reductions (mean -2.8 kg). Conversely, triple combinations with sulfonylureas were associated with weight gain (mean +2.5 kg).

These are consistent with the reported weight-loss benefits of SGLT2 inhibitors and potential weight gain with sulfonylureas. [Acta Endocrinol (Buchar) 2022;18:216-224; Adv Ther 2018;36:44-58]

No major adverse events were reported.

Takeaways

T2D frequently co-exists with hypertension and dyslipidaemia, requiring multiple medications that reduce patient adherence and therapeutic outcomes. Fixed-dose combinations offer advantages, including reduced pill burden, improved compliance, and synergistic effects. [J Family Med Prim Care 2020;9:5450-5457; Drugs Real World Outcomes 2023;11:167-176]

“[We] analysed the real-world effectiveness of various fixed-dose combinations in achieving glycaemic control and managing comorbidities in T2D patients. [We found that] multidrug combinations demonstrated superior efficacy over dual therapy in T2D management,” said Patel.

“This real-world evidence strongly advocates for aggressive multidrug combination approaches as the preferred strategy in T2D patients with inadequate glycaemic control, fundamentally shifting diabetes management toward comprehensive combination-first protocols,” Patel continued.