An Observational Study to Evaluate the Effect of Vildagliptin Compared to Glimepiride on Glycemic Control and Lipemia in Type 2 Diabetes Patients

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by impaired regulation and utilization of glucose, leading to hyperglycemia. Persistent elevated blood glucose levels are associated with long-term complications, including damage to the immune system, neurological function, and vascular health. The pathophysiology of T2DM is primarily attributed to two mechanisms: inadequate insulin secretion by the pancreas and cellular insulin resistance. In this condition, the pancreas fails to produce sufficient insulin, and the body’s cells exhibit diminished responsiveness to insulin, resulting in impaired glucose uptake (1).The rising prevalence of T2DM has been strongly linked to urbanization, lifestyle changes, and poor dietary habits. In the past, T2DM was predominantly observed in older adults; however, the increasing rates of obesity, physical inactivity, and poor nutrition have significantly contributed to the growing incidence of T2DM in children, adolescents, and young adults. Obesity and excess adiposity are particularly crucial factors in the development of T2DM. Furthermore, the progression of endothelial dysfunction, which can lead to peripheral artery disease (PAD), stroke, and dyslipidemia, is common in individuals with T2DM, contributing to the heightened risk of cardiovascular disease and mortality. Thus, controlling lipid profiles and maintaining optimal glycemic control are critical for reducing cardiovascular complications in T2DM patients (2).Due to the close association between lipid metabolism and glycemic regulation, special attention must be given to both factors to prevent microvascular and macrovascular complications. Metformin, a first-line therapy for T2DM, increases insulin sensitivity and reduces insulin resistance. It remains one of the most widely used oral medications in T2DM management. Another commonly used class of drugs, sulfonylureas, such as glimepiride and tolbutamide, stimulate the pancreas to increase insulin production. Glimepiride, a second-generation sulfonylurea, acts by binding to ATP-sensitive potassium channels in pancreatic β-cells, thereby enhancing both first-phase and second-phase insulin secretion (3).Advances in the understanding of T2DM pathophysiology have led to the development of novel pharmacological therapies. Incretin enhancers, particularly dipeptidyl peptidase-4 (DPP-4) inhibitors, such as sitagliptin and vildagliptin, function by inhibiting the breakdown of incretin hormones, including glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). These hormones play a pivotal role in glucose regulation by stimulating insulin secretion and inhibiting glucagon release, especially in response to meals. DPP-4 inhibitors maintain the activity of these incretin hormones, thereby improving glycemic control. Moreover, DPP-4 inhibitors have been shown to lower adipocytokine levels, protect β-cell function, reduce insulin resistance, and mitigate lipotoxicity, contributing to better glucose and lipid homeostasis (4). Furthermore, DPP-4 inhibitors, particularly vildagliptin, have demonstrated a reduction in glucagon release during fasting and postprandial states, improving insulin sensitivity. This mechanism of action has made DPP-4 inhibitors an attractive option for managing T2DM, as they provide a balanced approach to both hyperglycemia and dyslipidemia (5).

EPIDEMIOLOGY:

The International Diabetes Federation (IDF)  reports that in 2025, an estimated 1 in 9 adults (589 million) globally are living with diabetes. The IDF Diabetes Atlas projects that by 2050, this number will rise to 1 in 8 adults, totaling 853 million. A significant portion, over 40%, of those with diabetes are unaware of their condition (6).

ETIOLOGY:

The development of Type 2 diabetes mellitus (T2DM) is primarily driven by insulin resistance and β-cell dysfunction. Obesity, especially excess visceral fat, is a key contributor. Other risk factors include prehypertension, hypertension, excess growth hormone, and conditions like gestational diabetes, Cushing’s syndrome, and polycystic ovary syndrome (PCOS). Genetic predisposition also plays a significant role in the onset of T2DM (7).

SIGNS AND SYMPTOMS:

Common signs and symptoms of Type 2 diabetes include polyuria (frequent urination), fatigue, blurred vision, and numbness or tingling in the feet or hands. Patients may also experience slow-healing sores, unexplained weight loss, polydipsia (excessive thirst), and dry mouth (8).

PATHOPHYSIOLOGY:

Type 2 diabetes is characterized by insufficient insulin secretion from the pancreatic β-cells and peripheral insulin resistance. This resistance results in impaired glucose uptake by muscle cells, augmented hepatic glucose production, and increased lipolysis. It is often associated with elevated plasma levels of inflammatory cytokines and free fatty acids. The role of dysregulated glucagon secretion is particularly critical. In T2DM, the reciprocal relationship between the insulin-producing β-cells and the glucagon-releasing α-cells is disrupted, leading to elevated blood glucose and glucagon concentrations. When the α-cells responsible for glucagon secretion are impaired or lost, it results in further elevations in both blood glucose and glucagon levels, exacerbating the hyperglycemic state (9).

TREATMENT AND MANAGEMENT:

Management of Type 2 diabetes involves lifestyle changes and pharmacological interventions. Key strategies include regular exercise, weight loss, blood sugar monitoring, and healthy eating. Pharmacological treatments include sulfonylureas (e.g., glimepiride, glipizide), meglitinides (e.g., repaglinide, nateglinide), and GLP-1 receptor agonists (e.g., exenatide). DPP-4 inhibitors (e.g., sitagliptin, vildagliptin) enhance insulin secretion, while metformin, a biguanide, improves insulin sensitivity. Thiazolidinediones (e.g., pioglitazone) and α-glucosidase inhibitors (e.g., acarbose) also help manage blood glucose.  SGLT-2 inhibitors (e.g., dapagliflozin) (10).

MATERIALS AND METHODOLOGY:

• This study was conducted in the Department of General Medicine at Durgabai Deshmukh Hospital and Research Centre (DDHRC), Vidyanagar, Hyderabad, over a period of 6 months.
• A comparative and prospective study was conducted on 80 patients above 30 years with Type 2 diabetes mellitus patients who were on Glimepiride monotherapy or Glimepiride + Metformin therapy; Vildagliptin monotherapy or Vildagliptin + Metformin therapy of at least up to two years..
• Data collection was based on patient reports, and statistical analysis was performed  Mean ± SD was used to display continuous variables. To measure statistical significance, we used the Student t-test to compare two Three consecutive means were compared using one-way analysis of variance (ANOVA). We used SPSS 26.0.

RESULTS AND DISCUSSION:

80 subjects with type 2 diabetes mellitus were included in the study from the general medicine department of Durgabhai Deshmukh Hospital over six months, following specific inclusion and exclusion criteria.

1. Distribution of subjects based on Age:

Our study includes total of 80 subjects. Average age of total patients is 66.26. In which majority of subjects were above age of 70 (43. 8%)

2: Table shows distribution of patients based on gender

In a total of 80 subjects, 36 were found to be male and 44 were found to be females. Our study shows female predominance.

3: Distribution of subjects based on treatment.

In a total of 80 subjects, 50 patients were found to be treated with glimepiride and 30 patients were found to be treated with vildagliptin. Our study shows vildagliptin predominance.

4: COMPARISION OF MEAN AND STANDARD DEVIATION DIFFERENCE OF SUBJECTS

Fig  4: graph represent the comparison of mean difference of subjects treated with glimepiride and vildagliptin, Over a period of 6 months

1. Mean difference of FBS of vildagliptin treated patients is 131 and mean difference of FBS of glimepiride treated patients is 70 and (P value is 0.016) not significant
2. Mean difference of PPBS of vildagliptin treated patients is 167 and mean difference of PPBS of glimepiride treated patients is 32 and (P value is 0.001) it is significant
3. Based on above comparison vildagliptin treated patients FBS,PPBS shows more difference.

5. COMPARISION OF BMI MEAN DIFFERENCE IN SUBJECTS

Fig 5: Bar graph represents the comparison of BMI in patients treated with vildagliptin compared with glimepiride treated patients over a 6 months interval BMI mean difference compared .

1. The mean difference of BMI in patients using vildagliptin is 4.29
2. The mean difference of BMI in patients using glimepiride is 0.18
3.  Based on above comparison vildagliptin using patients shows more difference in BMI than glimepiride using patients (P <0.01)

6. COMPARISION OF MEAN DIFFERENCE OF LIPID PROFILE OF SUBJECTS

Fig 6 : graph represents the comparison of mean difference of lipid profile of patient using vildagliptin vs patients using glimepiride over 6 months

lipid profile comparison between glimepiride and vildagliptin patients shows that the vildagliptin has a larger mean difference. Compared to glimepiride, it reduces lipid abnormalities more effectively.

7. COMPARISION OF HBA1C LEVLES IN SUBJECTS

Fig 7: graph represent the comparison of HBA1C level in patients treated with vildagliptin and patient treated with Glimepiride over 6 months mean difference is compared

1. Mean difference of HBA1C in vildagliptin treated patients is 10.08
2. Mean difference of HBA1C in Glimepiride treated patients is 7.78

8. SUBJECTS OVERALL MEAN DIFFERENCE OF ALL PARAMETERS BY AGE

Fig 8: Graph represent the comparison of all parameter levels in patients treated with vildagliptin and patients treated with glimepiride over the age groups <60 years. Vildagliptin shows significant reduction.

9. SUBJECTS OVERALL MEAN DIFFERENCE OF ALL PARAMETERS BY AGE 60 – 70 YEARS

Fig 9: Graph represent the comparison of all parameter levels in patients treated with vildagliptin and patients treated with glimepiride over the age groups 60-70 years.

10. SUBJECTS OVERALL MEAN DIFFERENCE OF ALL PARAMETERS BY AGE ABOVE 70 YEAR

Fig 10: Graph represent the comparison of all parameter levels in patients treated with vildagliptin and patients treated with glimepiride over the age groups >70 years

11.MEAN DIFFERENCE OF LIPID PROFILE OF SUBJECTS

Fig 11: graph represents the comparison of mean difference of lipid profile of patient using vildagliptin vs patients using glimepiride over 6 months.  comparison shows that vildagliptin has a larger mean difference. Compared to glimepiride, it reduces lipid abnormalities more effectively.

12. SUBJECTS OVERALL MEAN DIFFERNCE OF ALL PARAMETERS IN MALE

Fig 11. Graph comparison of decreased in overall parameters (FBS, PPBS, BMI, TC, LDL, HDL, TG, HbA1C) according to gender treated with both vildagliptin and Glimepiride from 3 months to 6 months

In vildagliptin treated patient’s male patient’s parameters (FBS, PPBS,TC,BMI) reduced more and difference is seen in male.

13. SUBJECTS OVERALL MEAN DIFFERNCE OF ALL PARAMETERS IN FEMALE

Fig 13: Bar graph represents the reduced level of all parameters in vildagliptin treatment is more than glimeperide treatment