Type 2 diabetes has become one of Pakistan’s most pressing public health challenges. Poor glycemic control is common among Pakistani patients, driven by a combination of late diagnosis, limited access to newer therapies, dietary patterns, and constrained healthcare resources. While randomized controlled trials have established the glycemic, cardiovascular, and renal benefits of SGLT2 inhibitors in carefully selected populations, clinicians in countries like Pakistan have lacked robust local data confirming that these benefits translate to routine practice, where patients are older or younger, sicker or healthier, and less closely monitored than trial volunteers.

The new study was designed specifically to fill that gap. Conducted as an open-label, prospective, observational post-marketing surveillance study and registered on ClinicalTrials.gov (NCT05164263), it enrolled adults aged 18 to 65 years with type 2 diabetes whose glycemic control was inadequate, defined as a glycated hemoglobin (HbA1c) between 7 and 10 percent, and whose kidney function was reasonably preserved, with an estimated glomerular filtration rate (eGFR) above 60 mL/min/1.73 m². Physicians prescribed empagliflozin at 10 mg or 25 mg, either alone or in a fixed combination with metformin, according to their clinical judgment, and patients were followed for six months with scheduled assessments of glycemic and metabolic parameters.

The scale of the study lends it weight. A total of 952 participants were enrolled across sites ranging from major academic centers such as King Edward Medical University in Lahore and Dow University of Health Sciences in Karachi to community diabetes clinics in Rawalpindi, Sialkot, Peshawar, and Hyderabad. Of these, 765 participants, or 80.4 percent, completed the full six-month follow-up, a retention rate that strengthens confidence in the results. The researchers analyzed effectiveness using a modified intention-to-treat approach, handling missing follow-up values with the last observation carried forward method, a pragmatic choice common in real-world surveillance research.

The headline result concerns HbA1c, the standard long-term marker of blood glucose control. Median HbA1c fell from 8.8 percent at baseline to 7.4 percent at six months, a statistically significant improvement that moved the typical patient from poorly controlled diabetes to near-target levels. Notably, the combination therapy outperformed monotherapy: patients taking empagliflozin plus metformin achieved a median HbA1c reduction of 1.10 percentage points, compared with 0.60 percentage points for those on empagliflozin alone, a difference that was highly significant. This pattern makes physiological sense, since the two drugs attack hyperglycemia through complementary mechanisms.

That mechanistic complementarity is worth unpacking. Metformin, the decades-old first-line drug for type 2 diabetes, works primarily by reducing glucose production in the liver and improving insulin sensitivity in peripheral tissues. Empagliflozin operates entirely differently: it blocks SGLT2 proteins in the proximal tubules of the kidney, preventing the reabsorption of filtered glucose and flushing excess sugar out of the body through the urine. Because this route of glucose excretion is independent of insulin, SGLT2 inhibitors lower blood sugar even in insulin-resistant patients, and the caloric loss through urine contributes to weight reduction. The dual action explains why the combination arm achieved deeper glycemic gains in this study.

Beyond blood sugar, the metabolic ripple effects were consistent with the drug’s known pharmacology. Median body weight dropped from 77.0 kilograms to 75.0 kilograms over the six months, a modest but meaningful reduction given that even small sustained weight losses improve insulin sensitivity and cardiovascular risk. Systolic blood pressure and fasting blood glucose also declined significantly. Encouragingly for a drug class that acts on the kidney, renal parameters remained stable throughout the study, and eGFR actually rose slightly over the follow-up period, a pattern consistent with the hemodynamic effects SGLT2 inhibitors exert within the kidney’s filtration apparatus and with the renal protection demonstrated in dedicated outcome trials.

Safety, the other half of the post-marketing equation, was equally reassuring. Hypoglycemia was uncommon and became rarer over time, falling from 1.9 percent of participants at one month to just 0.5 percent at six months. This low rate reflects an important property of SGLT2 inhibitors: because they remove glucose through the urine rather than forcing it into cells, they rarely drive blood sugar dangerously low, especially when not combined with insulin or sulfonylureas. Serious adverse events were rare, occurring in only 0.5, 0.4, and 0.3 percent of participants at the successive follow-up visits, and adverse events overall were generally mild and diminished as the study progressed.

The study’s authors, led by Muhammad Umar Wahab of the Umar Diabetes Foundation in Islamabad, together with colleagues from nineteen institutions across Pakistan, conclude that in routine clinical practice empagliflozin alone and in combination with metformin was generally well tolerated and associated with improvements in glycemic control, body weight, and blood pressure, with preserved renal function over six months. The research adhered to the Declaration of Helsinki and international good clinical practice guidelines, with ethics approval from the Advanced Educational Institute and Research Center and informed consent obtained from all participants. The authors declared no competing interests, and the work received no dedicated funding, though the authors acknowledged technical support from the Medical Affairs department of Getz Pharma, the manufacturer of the Diampa formulations studied.

For global health observers, the significance of this study extends well beyond one drug in one country. Real-world evidence from low- and middle-income countries has been persistently thin, meaning that treatment guidelines for hundreds of millions of diabetic patients are often extrapolated from trials conducted in wealthy health systems with different diets, genetic backgrounds, comorbidity patterns, and monitoring capabilities. By demonstrating that empagliflozin performs as expected in Pakistani clinical practice, with effectiveness and safety figures that mirror the international trial literature, the study provides local validation that could encourage wider adoption of SGLT2 inhibitors across South Asia. As diabetes prevalence continues to climb in the region, such locally grounded evidence may prove as consequential as any laboratory breakthrough, translating decades of molecular kidney physiology into measurable improvements in the daily management of a disease that now touches one in ten adults worldwide.

Subject of Research: Real-world safety and effectiveness of empagliflozin with or without metformin in Pakistani adults with type 2 diabetes

Article Title: Real-world safety and effectiveness of empagliflozin (Diampa®) alone or in combination with metformin (Diampa-M®) in patients with type 2 diabetes mellitus in Pakistan: a multicenter observational study

Article References: Wahab, M. U., Bhalli, A., Mehmood, H., Shaukat, I., Umar, A., Lohano, V., Ahmed, S., Hasan, M., Tahir, S., Nawaz, A., Iqbal, M., Hadi, A., Safi, A. U. K., Siddiqui, A., Bhatti, I., Saghir, M., Ahmad, M., Ahmad, W., Khan, J. K., & Tahir, M. N. (2026). Real-world safety and effectiveness of empagliflozin (Diampa®) alone or in combination with metformin (Diampa-M®) in patients with type 2 diabetes mellitus in Pakistan: a multicenter observational study. BMC Endocrine Disorders. https://doi.org/10.1186/s12902-026-02552-z

Image Credits: AI Generated

DOI: 10.1186/s12902-026-02552-z

Keywords: type 2 diabetes, empagliflozin, metformin, SGLT2 inhibitors, HbA1c, post-marketing surveillance, Pakistan, real-world evidence, glycemic control, hypoglycemia, renal function, observational study