Type 2 Diabetes Mellitus (T2DM) is a complex metabolic disorder characterized by chronic hyperglycemia resulting from a combination of insulin resistance and β-cell dysfunction1. It is a significant public health concern globally, with increasing prevalence, particularly in developing countries like India2. Effective glycemic control is essential to reduce the risk of diabetes-related complications, including cardiovascular disease, nephropathy, neuropathy, and retinopathy3,4.

Management of T2DM typically involves lifestyle modifications, oral hypoglycemic agents (OHAs), and injectable therapies, depending on the severity and progression of the disease5. Among the available therapeutic options, dipeptidyl peptidase-4 (DPP-4) inhibitors, such as Sitagliptin, and glucagon-like peptide-1 (GLP-1) receptor agonists, such as Liraglutide, have gained prominence for their efficacy in glycemic control and additional metabolic benefits6.

Sitagliptin, a DPP-4 inhibitor, improves glycemic control by enhancing endogenous incretin activity, thereby promoting insulin secretion and reducing glucagon levels. It is well-tolerated and preferred in patients requiring an oral agent with minimal side effects7,8. In contrast, Liraglutide, a GLP-1 receptor agonist, exerts its effects by mimicking endogenous GLP-1, enhancing glucose-dependent insulin secretion, delaying gastric emptying, and inducing satiety, which often leads to significant weight loss.

While both medications target the incretin pathway, their mechanisms of action, efficacy, and safety profiles differ. In resource-limited settings like India, where cost and accessibility often influence treatment decisions, it is crucial to compare the effectiveness and tolerability of these agents to guide clinical practice.

This observational study aimed to evaluate and compare the efficacy and safety of Sitagliptin and Liraglutide in patients with T2DM, focusing on glycemic control, weight reduction, and adverse events over a 12-week period. The findings aim to provide insights into optimal therapeutic choices tailored to patient-specific needs and resource availability.

Study Design and Setting:

This observational study was conducted at Dr. Vitthalrao Vikhe Patil Foundation's Medical College and Hospital, Ahilyanagar, Maharashtra, over a period of one year, from November 2023 to October 2024.

Study Population:

The study included 100 adult patients diagnosed with Type 2 Diabetes Mellitus (T2DM) attending the outpatient department of the hospital. Patients were divided into two groups:

Sitagliptin group (n=50): Patients receiving Sitagliptin 100 mg once daily.

Liraglutide group (n=50): Patients receiving

Liraglutide subcutaneous injection at a dose titrated up to 1.8 mg/day.

Inclusion Criteria:

Adults aged 18–65 years.

Diagnosed with T2DM with HbA1c levels between 7% and 10%.

On stable antidiabetic therapy for at least 3 months before enrollment.

Exclusion Criteria:

Type 1 diabetes or other forms of diabetes.

Pregnant or lactating women.

Severe renal impairment (eGFR < 30 mL/min/1.73 m²).

History of pancreatitis or thyroid carcinoma.

Allergy or intolerance to Sitagliptin or Liraglutide.

Study Procedure:

Baseline clinical parameters, including HbA1c, fasting blood glucose (FBG), postprandial blood glucose (PPBG), and body weight, were recorded for all participants at the start of the study. Patients were followed up at 4-week intervals, and final assessments were conducted at the end of 12 weeks.

Outcome Measures:

Primary Outcome:

Reduction in HbA1c from baseline to 12 weeks.

Secondary Outcomes:

Changes in FBG and PPBG levels.

Weight reduction.

Incidence of adverse events, including gastrointestinal disturbances and hypoglycemia.

Data Collection and Statistical Analysis:

Data were collected using a standardized case record form. Continuous variables (e.g., HbA1c, FBG, PPBG, and weight) were expressed as mean ± standard deviation, and categorical variables (e.g., adverse events) were expressed as proportions. Statistical analysis was performed using SPSS version 25.0. Independent t-tests were used to compare continuous variables between the two groups. Chi-square tests were used for categorical variables. A p-value < 0.05 was considered statistically significant.

Ethical Considerations:

The study Ethical approval was obtained from the Institutional Ethics Committee of DVVPF's Medical College and Hospital before the commencement of the study. All participants provided written informed consent after being fully informed about the study's objectives, procedures, potential benefits, and risks.

Demographic Characteristics

The study enrolled 100 patients diagnosed with Type 2 Diabetes Mellitus (T2DM), equally divided between the Sitagliptin group (n=50) and the Liraglutide group (n=50). The mean age of the study population was 56.2 ± 10.4 years, with no statistically significant difference between the two groups (p = 0.32). The gender distribution was comparable, with males comprising 56% of the Sitagliptin group and 60% of the Liraglutide group (p = 0.48), as shown in Table 1.

Table 1: Demographic Characteristics

Figure No:1. Demographic Characteristics

Baseline Clinical Parameters

At baseline, the mean HbA1c was 8.5 ± 1.2%, and the mean fasting blood glucose (FBG) and postprandial blood glucose (PPBG) were 160 ± 30 mg/dL and 210 ± 45 mg/dL, respectively. There were no statistically significant differences between the two groups in HbA1c (p = 0.40), FBG (p = 0.50), or PPBG (p = 0.45), as outlined in Table 2.

Table 2: Baseline Clinical Parameters

Figure No:2. Baseline Clinical Parameters

Changes in Glycemic Parameters After 12 Weeks

After 12 weeks of treatment, the Liraglutide group showed a significantly greater reduction in HbA1c (1.2 ± 0.4%) compared to the Sitagliptin group (0.8 ± 0.3%) (p = 0.01). Similarly, reductions in FBG (40 ± 15 mg/dL vs. 25 ± 10 mg/dL, p = 0.02) and PPBG (60 ± 25 mg/dL vs. 40 ± 20 mg/dL, p = 0.01) were significantly greater in the Liraglutide group (Table 3).

Table 3: Changes in Glycemic Parameters After 12 Weeks

Figure No: 3. Changes in Glycemic Parameters After 12 Weeks

Weight Reduction

The Liraglutide group demonstrated a significantly greater weight reduction (3.8 ± 1.2 kg) compared to the Sitagliptin group (1.5 ± 0.5 kg) (p < 0.001), as detailed in Table 4.

Table 4: Weight Reduction After 12 Weeks

Figure No: 4. Weight Reduction After 12 Weeks

Adverse Events and Safety Profile

Mild gastrointestinal disturbances were reported in 10% of the Sitagliptin group and 20% of the Liraglutide group, with the difference being statistically significant (p = 0.04). Hypoglycemic episodes were observed in 2% of patients in the Sitagliptin group and 4% in the Liraglutide group, though the difference was not statistically significant (p = 0.58). These findings are summarized in Table 5.

Table 5: Adverse Events and Hypoglycemia

Figure No: 5. Adverse Events and Hypoglycemia

The present observational study compared the efficacy and safety of Sitagliptin, a DPP-4 inhibitor, and Liraglutide, a GLP-1 receptor agonist, in the management of Type 2 Diabetes Mellitus (T2DM). Our findings revealed that Liraglutide demonstrated superior glycemic control and weight reduction compared to Sitagliptin, although it was associated with a higher incidence of mild gastrointestinal side effects.

Glycemic Control

Liraglutide significantly reduced HbA1c, fasting blood glucose (FBG), and postprandial blood glucose (PPBG) levels compared to Sitagliptin. These findings are consistent with studies conducted by Zang et al8. (2016), Li et al9. (2017), and Pratley et al10. (2010), which demonstrated the potent glucose-lowering effects of GLP-1 receptor agonists. The superior efficacy of Liraglutide is attributed to its ability to enhance glucose-dependent insulin secretion, suppress glucagon release, and delay gastric emptying. Conversely, Sitagliptin, as a DPP-4 inhibitor, primarily increases endogenous incretin levels, resulting in less pronounced glycemic control compared to GLP-1 receptor agonists (Zang et al8., 2016; Lind et al11., 2016).

The differences in mechanisms of action between these agents likely explain the variation in their efficacy. Liraglutide appears to be a better option for patients requiring tighter glycemic control, particularly those with higher baseline HbA1c levels, as observed in the LEAD-2 trial conducted by Nauck et al12. (2009).

Weight Reduction

Liraglutide was associated with significantly greater weight reduction compared to Sitagliptin. Similar observations were reported in the studies by Li et al9. (2017) and Lind et al11. (2016), which highlighted the anorectic effects of Liraglutide mediated through central GLP-1 receptors, leading to reduced appetite and caloric intake. Weight reduction is a critical factor in T2DM management, as it improves insulin sensitivity and lowers cardiovascular risk. On the other hand, Sitagliptin, being weight-neutral as demonstrated in prior studies (Zang et al8., 2016; Nauck et al13., 2014), may not be the preferred choice for patients prioritizing weight management.

Safety and Tolerability

Both Sitagliptin and Liraglutide were found to be safe and well-tolerated overall. However, Liraglutide was associated with a higher incidence of mild gastrointestinal disturbances, such as nausea and vomiting, which are well-documented side effects of GLP-1 receptor agonists (Pratley et al10., 2010; Lind et al11., 2016). These adverse effects are generally transient and resolve with continued therapy. The incidence of hypoglycemia was low and comparable between the two groups, consistent with findings from previous studies (Nauck et al13., 2014; Ayesh et al14., 2024).

Clinical Implications

In resource-limited settings such as India, cost and accessibility are critical factors influencing the choice of antidiabetic agents. While Liraglutide offers superior glycemic control and weight reduction, its higher cost and subcutaneous mode of administration may restrict its use among certain populations (Li et al9., 2017; Nauck et al12., 2009). On the other hand, Sitagliptin, being an oral agent with a favorable safety profile, may be preferred by patients seeking convenience and affordability.

Limitations

This study had some limitations. Being observational, it did not allow for strict randomization, which could have introduced selection bias. The follow-up period of 12 weeks was relatively short, and longer-term studies are needed to evaluate sustained efficacy, safety, and patient adherence. Additionally, the sample size was modest and drawn from a single-center, limiting the generalizability of the findings.

This study demonstrated that Liraglutide is more effective than Sitagliptin in improving glycemic control and promoting weight reduction in patients with Type 2 Diabetes Mellitus (T2DM). Liraglutide significantly reduced HbA1c, fasting blood glucose, and postprandial blood glucose levels, while also achieving greater weight loss. However, its use was associated with a higher incidence of mild gastrointestinal side effects, which were transient. Sitagliptin, being weight-neutral and associated with minimal adverse events, remains a convenient and well-tolerated oral option. Treatment decisions should be individualized, considering patient-specific needs, affordability, and accessibility. While Liraglutide may be preferred for patients requiring enhanced glycemic control and weight management, Sitagliptin offers a suitable alternative for patients prioritizing simplicity and tolerability.

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