European Journal of Cardiovascular Medicine

Modern public health is concerned about the rising prevalence of diabetes. From 537 million in 2021 to 700 million in 2045, the International Federation of Diabetes [1] reports a large increase. Metabolic complications increase mortality, morbidity, and healthcare costs and raise the chance of catastrophic sequelae such cardiovascular disease, kidney failure, neuropathy, and blindness. With 90% to 95% of all cases being type 2 diabetes, it is by far the most common variety. T2DM differs from type 1 (autoimmune pancreatic beta cell destruction) in that it is defined by insulin resistance, progressive beta-cell failure, and impaired glucose metabolism. The cornerstone of treatment is a shift in lifestyle, which includes food and physical activity. [2]. However, pharmacological treatment is usually needed to manage glycaemia and prevent long-term effects. Due to T2DM complexity and diversity, antidiabetic medicines have increased in recent decades [3]. Many patients still take metformin as their first-line agent due to its low cost, safety, and efficacy. Despite its association with hypoglycaemia and weight gain, sulfonylureas are widely used worldwide and were once the preferred treatment [4]. New classes like Dipeptidyl Peptidase-4 (DPP-4) inhibitors offer modest glycaemic efficacy and low side effects, but their long-term effects are unclear. Clinical interest has grown in sodium-glucose cotransporter-2 (SGLT2) inhibitors because they lower blood glucose and preserve the heart and kidneys [5]. Glucagon-Like Peptide-1 (GLP-1) receptor agonists have also been highlighted for their capacity to lower blood sugar and improve obesity and cardiovascular health. Insulin therapy is important for people whose condition has progressed or who do not respond to oral and injectable non-insulin drugs.

Despite the variety of treatments, doctors struggle to choose the right one for each patient [6,7]. Efficacy in decreasing HbA1c, risk of hypoglycaemia, weight impact, acceptability, cost, concomitant conditions, and patient choice influence decision-making [8,9]. The ADA and EASD's clinical guidelines include extensive treatment protocols, however they are generally based on large-scale clinical trials that may not account for modest demographic differences. Another gap is the dearth of head-to-head comparisons across treatment classes; most pivotal studies instead matched new medications to placebo. Newer modules of medications, such as SGLT2 inhibitors and GLP-1 receptor agonists, have less data on efficacy and tolerability than earlier classes, such as metformin and sulfonylureas, in certain patient populations [10]. Despite this, these medications' cardiovascular benefits are well documented. More controlled clinical trials comparing pharmaceutical classes are needed due to a lack of comparative evidence. Methodically analysing each class of medications within the same patient group might illuminate their pros and cons [11]. This strategy outperforms global randomised controlled trials when healthcare priorities, patient demographics, and resources differ.

Therefore, this study evaluated 100 type 2 diabetics to determine antidiabetic medicine safety and efficacy. The study assessed glycaemic outcomes (lower HbA1c and fasting blood glucose levels) and safety outcomes (hypoglycaemia, weight changes, and adverse events. It compares insulin therapy, sulfonylureas, SGLT2 inhibitors, DPP-4 inhibitors, GLP-1 receptor agonists, and Metformin to get a better picture of treatment results. Meta-analyses and large-scale clinical trials have judged the efficacy and safety of many type 2 diabetes medications. According to seminal studies like the UK Retrospective  Diabetes Study (UKPDS), intense glycaemic therapy with sulfonylureas and insulin reduced microvascular consequences. Due to concerns regarding hypoglycaemia and weight gain, newer drug groups are being studied more. An intensive sulfonylurea regimen reduced nephropathy in the ADVANCE study, although not significantly lower cardiovascular events, emphasizing the limitations of older agents in comprehensive risk reduction.

In recent years, trials evaluating novel classes have reshaped treatment paradigms. The EMPA-REG OUTCOME study established that empagliflozin, an SGLT2 inhibitor, not only improved glycaemic parameters but also conferred significant cardiovascular and renal protective effects, a finding later supported by CANVAS and DECLARE-TIMI 58. Similarly, GLP-1 receptor agonists include liraglutide and the drug semaglutide, evaluated in the LEADER and SUSTAIN-6 trials, respectively, showed decreases in main adverse cardiovascular events, marking an important shift toward therapies with dual glucose-lowering and organ-protective properties. On the other hand, DPP-4 inhibitors, although generally safe and weight-neutral, have demonstrated more modest efficacy in HbA1c reduction, and their cardiovascular outcomes trials (such as SAVOR-TIMI 53 with saxagliptin) have largely shown neutrality, with some concerns regarding heart failure risk.

Study Design and Setting

This research employed a Retrospective observational design conducted in a Internal Medicine clinic in Prime Specialist Medical Center over one year. The objective was to compare antidiabetic drugs medication classes under routine clinical practice conditions. Patients were enrolled consecutively and followed at regular intervals for data collection and monitoring of outcomes.

Sample and Randomization

An overall of 100 adult affected roles diagnosed with T2DM were involved in the study. Each group of five received a different pharmaceutical class and twenty patients were randomly assigned:

1. Metformin
2. Sodium-Glucose Cotransporter-2 (SGLT2) inhibitors
3. Sulfonylureas
4. Dipeptidyl Peptidase-4 (DPP-4) inhibitors
5. Glucagon-Like Peptide-1 (GLP-1) receptor agonists

Randomisation ensured demographic and baseline clinical factors were evenly distributed between groups.

Inclusion Criteria

• Age between 30–70 years
• Confirmed diagnosis of T2DM
• Baseline glycated haemoglobin (HbA1c) levels > 7%

Exclusion Criteria

• Severe renal or hepatic impairment
• Secondary forms of diabetes
• Pregnancy or lactation
• Current insulin therapy at the time of recruitment

Outcome Measures

• Efficacy Outcomes: Primary endpoints included change in HbA1c from baseline, fasting plasma glucose, and postprandial glucose points noted at three and six months.
• Safety Outcomes: Secondary outcomes included adverse events, mild or severe hypoglycaemia, weight changes, and diabetic or pharmaceutical side effect hospitalisations. Adverse events were confirmed and documented using clinical interviews and patient records.

Statistical Analysis

To summarise the preliminary demographic and clinical data, descriptive statistics were used. For continuous variables like HbA1c and glucose levels, which are presented as mean ± standard deviation, researchers utilised ANOVA or independent t-tests to compare groups. The categorical variables of hypoglycaemia and adverse events were assessed with the Chi-square test. There was statistical significance when the p-value was less than 0.05. One well-known statistical program was used in the statistical analysis: SPSS v26.0.

Patient Demographics

An overall of 100 T2DM affected role were enrolled and evenly randomized across the five treatment groups (n=20 per group). The mean age of participants was 54.2 ± 8.6 years, with 52 males and 48 females. Baseline characteristics, including sex distribution, mean age, and initial HbA1c levels, were similar across groups with no statistically significant variances (p>0.05).

Table 1 Baseline Demographics details

Efficacy Outcomes

At six months, all drug classes demonstrated significant reductions in HbA1c linked to baseline (p<0.05 within groups). The greatest mean reduction was observed in the GLP-1 receptor agonist group (-1.6%), followed by SGLT2 inhibitors (-1.4%). Metformin achieved a reduction of -1.2%, similar to sulfonylureas (-1.3%), while DPP-4 inhibitors had the most modest effect (-0.9%). Fasting plasma glucose values showed a similar trend, with GLP-1 agonists and SGLT2 inhibitors achieving superior improvements.

Table 2 Mean HbA1c Reduction Across Groups at One Year

Safety Outcomes

Safety assessments revealed notable differences across drug classes. Hypoglycaemia was most frequent in the sulfonylurea group (25% of patients), followed by insulin-dependent rescue therapy cases in a few patients. GLP-1 and SGLT2 inhibitors caused weight gain reduction (mean -2.1 kg and -3.0 kg, respectively), while sulfonylureas and insulin resulted in modest weight gain (+1.8 kg and +2.4 kg). Gastrointestinal side effects were most common with metformin (15%), while genitourinary infections occurred in 10% of SGLT2 inhibitor users. Cardiovascular events were rare, with one nonfatal myocardial infarction reported in the sulfonylurea group.

Table 3 Frequency of Adverse Events Across Groups

Overall, the results recommend that SGLT2 inhibitors and GLP-1 receptor agonists offered the best balance between efficacy and safety, while sulfonylureas remained effective but carried a higher risk of hypoglycemia and weight gain. Metformin had common gastrointestinal adverse effects but was well-tolerated. DPP-4 inhibitors were moderately effective yet safe.

This research of 100 T2DM patients compared SGLT2 inhibitors, metformin, sulfonylureas, GLP-1 receptor agonists, and DPP-4 inhibitors. This six-month trial examines glycaemic management and safety to evaluate therapeutic drug efficacy. GLP-1 receptor agonists and SGLT2 inhibitors had the highest safety-effectiveness ratio; however, all pharmacological groups lowered HbA1c from baseline.

In this study HbA1c drops match large-scale experimental studies and meta-analyses. GLP-1 receptor agonists reduced haemoglobin A1c by 1.6% in our group, which is consistent with SUSTAIN-6 and LEADER trial results showing that liraglutide and semaglutide improved glucose control and cardiovascular health. The SGLT2 inhibitors' -1.4% drop matches the CANVAS and EMPA-REG OUTCOME trials' modest HbA1c reductions and significant cardiovascular and renal effects. DPP-4 inhibitors had a small effect (-0.9%), consistent with a previous study indicating that these drugs were glycaemic neutral in high-risk people (SAVOR-TIMI 53, EXAMINE, etc.) Sulfonylureas in our study produced a reduction of -1.3%, comparable to earlier findings from the UKPDS trial, which established their efficacy in lowering blood glucose but also highlighted the risk of hypoglycaemia [12]. Insulin, though not a primary comparison support in this study, remains the most potent glucose-lowering agent, yet its association with hypoglycaemia and weight gain has consistently limited its long-term acceptability as a first- or second-line therapy.

Table 4 Comparison of Existing Studies with the Present Study

Most Effective Drug Class

Among the drug classes compared, GLP-1 receptor agonists emerged as the most effective in reducing HbA1c, with additional benefits of weight reduction and a low incidence of hypoglycaemia. SGLT2 inhibitors were close in efficacy and provided significant metabolic and cardiovascular advantages. These findings reinforce existing clinical guidelines that increasingly recommend SGLT2 inhibitors and GLP-1 receptor agonists as second-line therapy, notably for cardiovascular or renal patients.

Metformin retained its role as a reliable baseline therapy, demonstrating solid efficacy and a favourable safety profile, albeit with higher gastrointestinal intolerance in a subset of patients. DPP-4 inhibitors, while safe and well tolerated, showed only modest efficacy, suggesting that they may be best suited for patients who cannot tolerate other therapies or as part of combination therapy when weight neutrality and low hypoglycaemia risk are prioritized.

Safety Considerations

Safety outcomes revealed important distinctions between the drug classes. Sulfonylureas were associated with the highest rate of hypoglycaemia (25%), reaffirming concerns reported in both the UKPDS and ADVANCE trials. This side effect poses a significant clinical challenge, particularly in elderly patients or those with comorbidities, where hypoglycaemia can increase cardiovascular risk.

GLP-1 receptor agonists and SGLT2 inhibitors demonstrated favourable safety profiles. The weight reduction observed in these groups (-3.0 kg and -2.1 kg, respectively) is particularly relevant in overweight and obese patients, where weight loss can improve both metabolic control and cardiovascular outcomes. However, gastrointestinal side effects were reported in the GLP-1 receptor agonist group (12%), consistent with previous reports. SGLT2 inhibitors were associated with genitourinary infections in 10% of patients, an expected class effect but generally manageable with appropriate patient counselling and monitoring.

Metformin was largely safe, though gastrointestinal side effects (15%) remain a well-recognized limitation, especially during initiation. DPP-4 inhibitors were generally well tolerated, with no significant increase in adverse events, confirming their safety profile reported in large-scale cardiovascular outcome trials.

Strengths of the Study

This study contributes meaningfully to the existing literature by providing a direct head-to-head comparison of multiple antidiabetic drug classes within the same patient cohort, something that is relatively uncommon in random assignment trials. Clinical studies are more likely to stand up in real life, making them directly applicable to everyday medical practice. Furthermore, the study’s balanced distribution of patients across drug classes and the inclusion of both efficacy and safety endpoints strengthen its clinical relevance.

Limitations

The sample size of 100 patients limits statistical power and generalisability. These results need bigger multicentre studies to confirm. Additionally, six months may not be long enough to detect long-term outcomes like cardiovascular events, chronic disease, or glycaemic control. Due to the study's single hospital, the sample population's variation may not be adequately reflected. The omission of insulin-treated patients limits findings on its therapeutic position compared to other pharmacological classes.

This research examined the efficiency and safety of five primary antidiabetic classes in 100 type 2 diabetics. All medication classes significantly reduced HbA1c, indicating improved glycaemic control. However, safety and therapeutic benefits differed. Combining GLP-1 receptor agonists and SGLT2 inhibitors produced the best balance, improving HbA1c, weight loss, and cardiovascular health (due to reduced hypoglycaemia and other side effects). Metformin was a reliable first-line medication, although sulfonylureas were effective but risked hypoglycaemia and weight gain. Due to their tolerability and low glycaemic impact, DPP-4 inhibitors may be used as adjuvants rather than principal therapies. These findings support the growing emphasis on individualised treatment approaches in clinical practice. Doctors should consider the patient's glycaemic goals, comorbidities, risk of adverse events, therapeutic goals, and other criteria before choosing a medication. Due to the minor sample size and quick follow-up, more large-scale, multicentre trials are required to validate these results and give long-term insights into comparative efficacy, safety, and cost-effectiveness across diverse populations.

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