Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder characterized by insulin resistance and β-cell dysfunction, leading to chronic hyperglycemia and an increased risk of both microvascular and macrovascular complications (1). With cardiovascular disease being the leading cause of mortality in T2DM patients, the focus of diabetes management has shifted beyond glycemic control to include cardiovascular risk reduction (2,3).

Sodium-glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are two novel classes of antihyperglycemic agents that have demonstrated cardiometabolic benefits in addition to lowering blood glucose (4,5). SGLT2 inhibitors, such as empagliflozin and dapagliflozin, function by inhibiting glucose reabsorption in the renal proximal tubule, promoting glycosuria and osmotic diuresis (6). These effects contribute to reductions in blood pressure, body weight, and heart failure hospitalizations, as shown in major cardiovascular outcome trials (7,8). On the other hand, GLP-1 RAs like liraglutide and semaglutide act by enhancing glucose-dependent insulin secretion, suppressing glucagon release, and delaying gastric emptying, with additional benefits on satiety and weight reduction (9,10). Their cardiovascular protective effects have also been well documented (11,12).

While both drug classes offer multifaceted advantages, direct head-to-head comparisons assessing their relative efficacy in real-world clinical settings remain limited. Understanding their comparative impact on glycemic parameters, cardiovascular risk markers, and adverse events is essential for personalized diabetes care. This study aims to evaluate and compare the efficacy of SGLT2 inhibitors versus GLP-1 receptor agonists in improving glycemic control and cardiovascular outcomes in patients with T2DM.

This prospective, randomized, open-label, parallel-group study was conducted over a period of 24 weeks at a tertiary care center. A total of 120 adult patients diagnosed with type 2 diabetes mellitus, aged between 40 and 65 years, were recruited. Eligibility criteria included HbA1c levels between 7% and 10%, stable antidiabetic background therapy (metformin monotherapy), and absence of recent cardiovascular events or renal impairment (eGFR < 60 mL/min/1.73 m²). Patients with type 1 diabetes, active infections, severe hepatic dysfunction, or pregnant/lactating women were excluded.

Participants were randomly allocated into two equal groups (n=60 each) using a computer-generated randomization list. Group A received empagliflozin 10 mg orally once daily (SGLT2 inhibitor), while Group B was administered liraglutide 1.2 mg subcutaneously once daily (GLP-1 receptor agonist). Both interventions were continued alongside standard care, including lifestyle counseling and metformin therapy.

Clinical and biochemical assessments were conducted at baseline and at the end of the 24-week follow-up. Parameters evaluated included glycated hemoglobin (HbA1c), fasting blood glucose (FBG), body weight, systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDL-C). Cardiovascular outcomes were monitored through documentation of major adverse cardiovascular events (MACE), which included myocardial infarction, stroke, and cardiovascular death.

Blood samples were collected following an overnight fast of 8–10 hours and analyzed using standardized laboratory techniques. Weight and blood pressure were measured using calibrated digital devices. Safety was evaluated by recording adverse events throughout the study period.

Statistical analysis was performed using SPSS version 26. Continuous variables were expressed as mean ± standard deviation. Intragroup comparisons were made using paired t-tests, while intergroup differences were assessed using independent t-tests and one-way ANOVA. A p-value of less than 0.05 was considered statistically significant.

A total of 120 patients were enrolled, with 60 patients in each group. The baseline characteristics were comparable between the two groups in terms of age, sex distribution, duration of diabetes, and baseline glycemic and cardiovascular parameters (Table 1).

After 24 weeks of treatment, both groups showed significant improvements in glycemic and cardiometabolic variables. The mean HbA1c in Group A (SGLT2 inhibitor) reduced from 8.2 ± 0.6% to 7.1 ± 0.4%, while in Group B (GLP-1 RA), it decreased from 8.3 ± 0.5% to 6.8 ± 0.3%. The difference between groups was statistically significant (p = 0.04) (Table 2).

Fasting blood glucose levels declined in both groups, with a greater reduction observed in Group B (−38.9 ± 7.5 mg/dL) compared to Group A (−31.5 ± 8.2 mg/dL, p = 0.03). Body weight also decreased more in Group B (−4.8 ± 1.2 kg) compared to Group A (−2.9 ± 1.0 kg, p < 0.01).

Systolic blood pressure and LDL-C showed greater reductions in the SGLT2 inhibitor group. SBP decreased by 11.5 ± 4.2 mmHg in Group A and by 6.3 ± 3.7 mmHg in Group B (p = 0.02). LDL-C was lowered by 19.2 ± 5.8 mg/dL in Group A and 12.6 ± 4.9 mg/dL in Group B (p = 0.03) (Table 2).

Three cardiovascular events were reported during the study: two in Group A and one in Group B. No significant adverse events requiring discontinuation were observed in either group.

Table 1: Baseline Characteristics of Participants

Table 1 shows no significant differences in baseline characteristics between the two groups (p > 0.05).

Table 2: Changes in Clinical Parameters at 24 Weeks

Table 2 indicates statistically significant improvements in all parameters in both groups, with varying magnitudes of effect.

This study compared the glycemic and cardiovascular efficacy of SGLT2 inhibitors and GLP-1 receptor agonists in patients with type 2 diabetes mellitus over a 24-week period. Both treatment groups showed significant improvements in glycemic control, weight reduction, and cardiovascular parameters, supporting previous findings on the multifactorial benefits of these drug classes (1–3).

The reduction in HbA1c was more pronounced in the GLP-1 RA group, consistent with earlier studies that reported superior glycemic control with liraglutide compared to SGLT2 inhibitors (4,5). The underlying mechanism involves GLP-1 mediated enhancement of insulin secretion and suppression of glucagon, especially in a glucose-dependent manner, which provides tight postprandial glucose regulation (6). Although SGLT2 inhibitors also lowered HbA1c effectively, their mechanism of promoting glucosuria may result in a ceiling effect in patients with lower baseline glucose levels (7).

In terms of weight loss, GLP-1 RAs again demonstrated greater efficacy, aligning with data from the LEAD and SCALE trials, where liraglutide significantly reduced body weight in obese and diabetic populations (8,9). This is attributed to their central appetite-suppressing effects and delayed gastric emptying (10). SGLT2 inhibitors also promote weight loss, largely via caloric loss through glycosuria, but this may be less effective in patients with compromised renal function (11).

Cardiovascular benefits were more pronounced in the SGLT2 inhibitor group, particularly regarding reductions in systolic blood pressure and LDL cholesterol. The EMPA-REG OUTCOME and CANVAS trials previously reported significant reductions in heart failure hospitalization and cardiovascular death with empagliflozin and canagliflozin (12,13). These effects may be due to their mild diuretic action, reduction in arterial stiffness, and favorable modulation of intraglomerular pressure (14). While GLP-1 RAs such as liraglutide also offer cardiovascular protection, the mechanism is likely related to anti-inflammatory and anti-atherogenic properties rather than hemodynamic changes (15).

Our findings further support the complementary roles of these agents in managing T2DM with coexisting cardiovascular risks. Although both drug classes demonstrated beneficial outcomes, individualized therapy based on comorbidities, tolerability, and patient preferences remains crucial. For instance, SGLT2 inhibitors may be preferred in patients with heart failure or chronic kidney disease, whereas GLP-1 RAs may be more suitable for those requiring greater weight reduction and glycemic control.

This study was limited by its relatively short duration, single-center design, and lack of double-blinding, which may introduce bias. Larger, long-term comparative trials are warranted to assess durability of effects, impact on cardiovascular events, and safety profiles in real-world settings.

Both SGLT2 inhibitors and GLP-1 receptor agonists offer significant glycemic and cardiovascular benefits in the management of type 2 diabetes mellitus. While GLP-1 RAs provide superior glycemic control and weight reduction, SGLT2 inhibitors demonstrate stronger effects on blood pressure and cardiovascular protection. Personalized treatment selection based on individual patient profiles remains essential for optimizing outcomes.

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