Calcutta School of Tropical Medicine

Fixed-dose combinations (FDCs) have become a mainstay in managing type 2 diabetes in India, offering potential benefits such as simplified regimens, improved adherence, and better glycemic control. However, several irrational FDCs—lacking validated pharmacodynamic synergy or compatible pharmacokinetic profiles—have raised serious safety concerns. In April 2025, the Central Drugs Standard Control Organisation (CDSCO) issued a regulatory ban on multiple antidiabetic FDCs, highlighting critical lapses in drug approval processes. To evaluate the regulatory and pharmacological rationale for the CDSCO’s ban, assess the evidence gaps in the banned FDCs and outline actionable strategies to strengthen FDC oversight in India and similar low- and middle-income countries (LMICs). This review synthesizes regulatory documentation from CDSCO, established pharmacodynamic synergy models (e.g., Chou-Talalay index, isobologram analysis), and clinical pharmacology literature. FDCs were evaluated for pharmacokinetic incompatibility, lack of synergy, overlapping toxicity, and regulatory bypass under the New Drugs and Clinical Trials Rules (2019). Most banned FDCs bypassed CDSCO review, gaining approval through state licensing authorities (SLAs) despite qualifying as “new drugs.” These combinations lacked synergy validation and often paired agents with overlapping toxicity profiles. The CDSCO’s regulatory intervention reasserts the importance of centralized approval, pharmacological compatibility, and scientific rigor in FDC evaluation. The ban marks a turning point in India’s approach to rational pharmacotherapy, with implications for regulatory harmonization, pharmacovigilance, and evidence-based prescribing. It serves as a model for LMICs aiming to balance accessibility with safety and scientific integrity in chronic disease management.

While broadly neutralizing antibodies (bnAbs) have been clinically shown to prevent HIV-1 acquisition, their relative effectiveness against regionally relevant HIV-1 forms is not clear. In the present study, we examined the extent of neutralization susceptibility of contemporary HIV-1 Indian clade C at a population level along with a head-to-head comparison with that from South Africa against a panel of clinically relevant best-in-class bnAbs. Env-pseudotyped viruses encoding HIV-1 India clade C env were found to be best neutralized by the V3 glycan-directed bnAbs (10-1074 and BG18) and select CD4 binding site (CD4bs)-directed bnAbs (VRC07, N6, and 1-18); however, they demonstrated significant resistance to V1/V2 apex-directed bnAbs. Interestingly, the magnitude of the neutralization sensitivity differed between contemporary India and South Africa clade C. Neutralization resistance to key bnAbs was observed to be associated with differences in residues on Env that form bnAb contact sites, gp120 loop lengths, and potential N-linked glycans. Notably, the second generation CD4bs bnAbs (VRC07, N6, 1-18) showed neutralization of VRC01- and 3BNC117-resistant viruses but with two- to sevenfold reduced potency compared to the VRC01-sensitive counterparts, likely due to the enrichment of resistance-associated residues observed in loop D. Predictive analysis indicated that the combination of BG18, N6, and PGDM1400 can provide over 95% neutralization coverage of contemporary India clade C at 1 µg/mL (IC80), an observation distinct from that observed with Africa clade C. Our study clearly highlights that both the complementarity of bnAb classes and the regionally relevant HIV-1 forms are important in achieving clinical effectiveness. IMPORTANCE While the development of vaccines to prevent HIV infection remains a global priority, their potential effectiveness is limited by the extraordinarily diversified circulating forms of HIV-1. The prospect of best-in-class broadly neutralizing antibodies (bnAbs) as a potential prevention option has been demonstrated in several studies, including the phase 2b Antibody-Mediated Prevention trials; however, to be broadly applicable, bnAbs will need to overcome the substantial variability of HIV env circulating globally, beyond the regions where efficacy trials are conducted. The present study highlights that the region-specific contemporary HIV-1 clade C viruses not only vary in their degree of susceptibility to the best-in-class clinically relevant bnAbs, but also are evolving at a population level to become increasingly resistant to the best-in-class bnAbs. Overall, the outcome of this study highlights the need for periodic assessment of sequence and neutralization profiles of the circulating regionally relevant HIV-1 forms toward prioritizing the bnAb combination suitable for effective intervention.

Objective The objective of this systematic review and meta-analysis (SRMA) was to evaluate the impact of electronic patient-reported outcomes (ePROs) on health-related quality of life (HRQoL) in patients with cancer. Design We performed SRMA of randomised controlled trials (RCTs) comparing ePRO interventions with usual care in patients with cancer. The primary outcome was HRQoL. We used a random effects model a priori due to the anticipated clinical heterogeneity. Subgroup analyses and meta-regressions were performed to explore sources of heterogeneity. After assessing the risk of bias using risk-of-bias tool (RoB V.2), we rated the evidence certainty using the Grading of Recommendations, Assessment, Development and Evaluations framework. Eligibility criteria We included studies meeting the following criteria: (1) RCTs; (2) patients diagnosed with any type of cancer, undergoing or having completed treatment; (3) comparing ePROs with usual care without ePRO interventions; (4) assessing the effect on HRQoL. Information sources We systematically searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials up to April 2024. Results We screened 7706 records to include 36 RCTs with 9608 patients. ePRO interventions showed a standardised mean difference (SMD) of 0.35; 95% CI 0.18 to 0.51 compared with usual care. Patients receiving ongoing therapy had an SMD of 0.39 (95% CI 0.21 to 0.58), while those who had completed therapy had an SMD of 0.12 (95% CI 0.01 to 0.22), with a significant subgroup difference (p=0.01). No statistically significant differences were observed across the method of ePRO assessment, cancer site, metastasis status, therapy status, average age or duration of ePRO use. The results remained consistent with Bayesian and other sensitivity analyses. Conclusions ePRO interventions improve HRQoL more than usual care in patients with cancer, with greater effect in those currently undergoing therapy. This improvement is independent of cancer type, duration of ePRO use or patient age. Future research should address sources of heterogeneity, explore long-term impacts and develop strategies to increase patient engagement and adherence to ePRO systems. PROSPERO registration number CRD42024531708.

A 44-year-old diabetic male presented with hypovolemic shock along with cough-cold, weakness, and low-grade fever for the past four months. On laboratory investigation, there were hyponatremia, hyperkalemia, and hypercalcemia. Persistently low parathyroid levels along with a positive ACTH stimulation test confirmed primary Addison's disease. On ultrasonography, there was a bilateral adrenal mass over which CT-guided FNAC was done. PAS stain of the sample showed intracellular yeast cells resembling histoplasmosis and on culture at 25°C it showed microconidia with successful conversion of mycelium to yeast. The patient was treated with Liposomal Amphotericin B over two weeks and steroids, with which the patient gradually improved.

Introduction Frailty and sarcopenia are prevalent syndromes among the elderly, significantly affecting health outcomes and quality of life. As major public health concerns, these conditions are associated with adverse outcomes, including falls, fractures, hospitalization, and increased mortality. This study investigates the prevalence of frailty and sarcopenia in the geriatric population and explores their correlation with socioeconomic and lifestyle factors. Materials and Methods An observational, cross-sectional study was conducted involving 180 geriatric patients. Data were collected through structured interviews and physical assessments, focusing on demographic details, medical history, and socioeconomic status. Frailty was assessed using the Fried frailty phenotype criteria, and sarcopenia was evaluated according to the European Working Group on Sarcopenia in Older People guidelines. Statistical analyses included t -tests and z -tests, with significance set at P ≤ 0.05. Results The prevalence of frailty was observed in 41.7% of participants, while 44.4% demonstrated signs of sarcopenia. The majority of participants were male (55.6%) and aged 60–70 years (72.2%). A significant association was found between frailty, sarcopenia, and chronic conditions such as hypertension (25.6%) and diabetes (18.9%), with 22.2% of participants suffering from both. Lifestyle factors revealed a predominantly nonvegetarian diet (95%) and a smoking prevalence of 17.2%. Socioeconomic factors, particularly occupation and gender, played a critical role in health outcomes, with a high proportion of female homemakers (33.3%) and retired individuals (30%). Conclusions The study underscores the substantial impact of frailty and sarcopenia on the geriatric population, highlighting the necessity for integrated healthcare strategies focusing on early detection and management. Addressing socioeconomic disparities and implementing lifestyle modifications are crucial for improving geriatric health outcomes. Future research should explore the biological mechanisms underlying these conditions and develop targeted interventions.

Visceral leishmaniasis (VL), caused by Leishmania donovani or Leishmania infantum , is prevalent in India and Brazil. Post-kala-azar dermal leishmaniasis (PKDL), a cutaneous form, can occur in patients who seem to have recovered from VL. The rK39 test, which detects circulating antibodies, shows high sensitivity and specificity for VL diagnosis in India, but its performance varies in other endemic regions, with a significant limitation being the inability to distinguish active disease from past infection. Herein, we investigated Aurora Kinase (LdAIRK), a conserved virulence factor across Leishmania species with a major role in cell division, for VL diagnosis. We analyzed serum samples from parasitologically confirmed symptomatic VL patients ( n = 79), PKDL patients ( n = 16), healthy controls, and other diseases ( n = 53) from India, along with VL patients ( n = 40) and healthy endemic controls ( n = 19) from Brazil, using enzyme-linked immunosorbent assay with rLdAIRK. The sensitivity of rLdAIRK was 98.73% (95% CI: 93.17–99.94) for Indian patients and 97.5% (86.84–99.94) for Brazilian patients. It also demonstrated a sensitivity of 93.75% (71.67–99.68) for Indian PKDL sera. Specificity ranged from 94.33% to 94.74% for Indian samples and 84.21% for Brazilian samples. Notably, LdAIRK showed low reactivity (8.3%) with follow-up patient samples compared with rK39 rapid diagnostic tests, indicating its potential as a test-of-cure tool. These findings were supported by dipstick and lateral flow tests (LFTs), which are user-friendly and suitable for field settings. We recommend incorporating recombinant antigen Ldairk in serological assays for the diagnosis of VL. IMPORTANCE An early detection and treatment of VL is essential in the control of this potentially fatal disease. Since signs and clinical symptoms of VL are non-specific, diagnosis is confirmed with serological tests. Rapid diagnostic tests (RDTs) against VL that detect antibodies are simple and field adaptable. rK39 antigen-based RDTs are in use, but their sensitivities vary in the different VL-endemic regions. Moreover, since the antibodies persist long after cure in healthy individuals, these RDTs cannot diagnose relapse of the disease. Here, we have identified a Ldairk as a new marker for the diagnosis of VL. We found that Indian VL and PKDL as well as Brazilian patient sera reacted to this protein consistently. Sensitivity was also maintained in the patient’s urine samples. Low reactivity with antibodies after cure with Ldairk can help distinguish previously treated cases from active and relapsed ones.

Context Nutritional status played significant roles in preventing infection of pathogens, expression of disease severity, and prognosis following treatment. Leishmaniasis is a neglected tropical disease affecting the poorest people and is generally undernourished. In the Indian subcontinent, malnutrition is found to be associated with visceral leishmaniasis (VL) but such reports for post kala-azar dermal leishmaniasis (PKDL) are not available. Objectives Assessment of nutritional status among PKDL cases from West Bengal, India. Methodology PKDL cases were searched by door-to-door visits. The nutritional status of the study participants was assessed by analyzing clinical, anthropometrical, and biochemical parameters. The data were analyzed using standard statistical methods with Minitab software. Results A total of 42 PKDL (Group A), 38 with VL history (Group B), and 80 healthy control participants (Group C) were included. We noticed a higher rate of ocular and dermal abnormalities due to Vitamin A deficiency among PKDL patients. A lower range of body mass index was recorded among both Group A and B. The mean hemoglobin and Vitamin B12 level of Group A were significantly lower than Group C. The mean white blood cell count was significantly higher in Group A than other two groups. Conclusion The study revealed that PKDL patients were undernourished as evident by few clinical, anthropometrical, and biochemical parameters. The initiative of providing nutrient-rich food during the treatment of leishmaniasis by the Government of West Bengal is justified. A case–control study is highly suggested to evaluate the impact of such food supply during treatment on disease prognosis.

Background Scrub typhus is an acute febrile illness that resembles other common febrile conditions such as leptospirosis, typhoid fever, malaria, and dengue. Recognizing its varied clinical manifestations, understanding associated epidemiological factors, and monitoring laboratory parameter changes are crucial for early differentiation from these disorders. Timely initiation of treatment with doxycycline ensures complete recovery from scrub typhus. Materials and Methods This observational cross-sectional study was conducted in the Department of Tropical Medicine, Kolkata, West Bengal, India on patients with a history of fever lasting more than 5 days, with or without rash and eschar, and confirmed positive for scrub typhus immunoglobulin M through enzyme-linked immunosorbent assay. The study included 30 patients aged over 12 years who were admitted to the School of Tropical Medicine, Kolkata, West Bengal, India. Results Most of the study population was between 21 and 50 years old, with females constituting 63.3% of cases. Rural residents accounted for 70% of the patients. The mean duration of fever at admission was 8.33 ± 1.58 days. The shock was observed in 16.7% of patients, of whom 40% responded to fluid therapy alone, whereas 60% required vasopressor support. Typically, shock develops around the eighth to ninth day of illness. Moderate pallor was seen in 90% of patients, and edema occurred in 16.7%. In 36.7% of patients, eschars were present, whereas 43.3% exhibited rashes. Lymphadenopathy was noted in 63.3%, and hepatosplenomegaly was identified in 56.7% of cases as mild and 23.3% as moderate—additionally, 6.7% of patients presented with ascites. Laboratory findings revealed leukocytosis in 60% of patients, thrombocytopenia in 6.7%, and an abnormal international normalized ratio in 6.7%. Elevated liver enzymes were detected in 50% of patients, whereas chest X-rays showed pneumonitis changes in the bilateral lower zones in 60%. Acute kidney injury (AKI) and acute meningoencephalitis were observed in 6.7% and 13.3% of patients, respectively. Doxycycline therapy elicited a positive response in 60% of patients within 48 h, whereas the remaining patients experienced a delayed response. Conclusion Scrub typhus is a significant cause of acute febrile illness with potential complications, including shock, pneumonitis, meningoencephalitis, and AKI. Clinical features such as eschars and rashes are pivotal for suspicion. Prompt diagnosis and treatment with doxycycline can significantly reduce morbidity and save lives.

Background & objectives This study was performed to assess the suitability of dried blood spot (DBS) samples for the serological screening of syphilis. Methods Two hundred paired DBS and plasma samples collected from six sexually transmitted infection (STI) clinics during the year 2023 were tested using three kits - Treponema pallidum haemagglutination assay (TPHA), Syphilis Total Ab and ErbaLisa Syphilis after standardization of the dilutions of the DBS elutes and considering the results of the paired plasma samples as a true status. Results The TPHA showed 89 per cent sensitivity and 100 per cent specificity, the EIA-Syphilis Total Ab. Kit showed 100 per cent sensitivity and 97 per cent specificity, whereas ErbaLisa syphilis showed 89 per cent sensitivity and 100 per cent specificity. However, one kit Syphilis ELISA (Oscar Medicare Pvt. Ltd., New Delhi) did not show agreement with the paired plasma samples at any dilution and was not considered suitable for the testing of DBS samples. The agreement between the plasma and DBS results was found to range from 94.5 to 98.5 per cent with a kappa agreement score of 0.89 for TPHA, ErbaLisa, and 0.97 for ELISA-Syphilis Total Ab. Interpretation & conclusions The findings of this study confirmed that the DBS samples can be used for the detection of anti-treponemal antibodies using the above-validated kits and thus may be a valuable tool in surveillance and epidemiological surveys conducted in India. The study also highlighted the need for validation of any plasma/serum syphilis antibody detection assay on DBS samples before using it on DBS samples

Currently, there are no clinically approved antiviral agents against dengue-virus (DENV). This study aimed to determine the prophylactic, antiviral, and therapeutic potential of quercetin by its pre-treatment, co-treatment, and post-treatment [24, 48, and 72 hours-post-infection (HPI)] of DENV-infected Balb/C mice through both oral and intraperitoneal (I.P) route, respectively. 80mg/kg/day and 16mg/kg/day of quercetin were non-toxic for oral and I.P administration, respectively. I.P. was found to be more effective than oral administration which significantly reduced DENV copy-number in co-treatment group (from day 1, p<0.01); post-treatment (24hpi),and pretreatment groups (day 3 onwards, p<0.05). Molecular-docking experiments indicated quercetin could act as a double-edged sword by strongly interacting with DENV envelope-glycoprotein (-8.1 kcal/mol) and NS5-RdRp domain (-8.0 kcal/mol), which are crucial for viral-attachment and replication. MD-simulation of docked complexes indicated their stability defined by low RMSD, RMSF, and stable H-bond with active-site residues. Significant reduction (p<0.001) in TNF-α, IL-6, ROS-production, and vascular leakage was observed among pre-, co-, and post-treatment (24 and 48 HPI) groups with promising hepatic and renal-protective effects. Pharmacological and functional-molecular interaction networks indicate a significant effect of quercetin on vascular integrity byVEGF-KDR signaling pathway (via PI3K-Akt and Ras signalling), oxygen homeostasis through HIF-1 signalling, and the anti-inflammatory response via PI3K-Akt, IL-6 and its receptor signalling (PPI enrichment P = 3.19e-10).Thus, it can be concluded that I.P. co- and post-treatment (24 hpi) of quercetin to DENV-infected mice could effectively reduce viral-titer, pro-inflammatory cytokines, ROS-response, and vascular permeability. Taken together this demonstrates quercetin as an important antiviral candidate against dengue.

Malaria and filariasis are mosquito-borne diseases caused by protozoal and nematode parasites, respectively. Despite different vectors, they can occur together under suitable conditions in endemic regions. In our case, microfilariae were incidentally discovered during a blood film examination for malaria. Accurate detection of microfilariae, especially in cases of low parasitemia, requires multiple blood smears and consideration of Wuchereria bancrofti's nocturnal periodicity, with blood collection ideally performed at night when parasitemia levels are highest. The presence of eosinophilia in our patient suggested a non-malarial parasitic infection, as eosinophilia is relatively uncommon in acute malaria. Our case highlights the need for a broad differential diagnosis, particularly in regions where both diseases are endemic and emphasise the value of detailed peripheral smear examinations to detect parasitic co-infections. Proper identification is essential for guiding tailored treatments in such complex cases.

OBJECTIVE: This study aimed to assess medication adherence and its association with quality of life (QoL) in type 2 diabetes (T2D) patients. MATERIALS AND METHODS: This cross-sectional study included 374 T2D patients aged 18–75 years, receiving treatment for at least six months. Medication adherence was evaluated using the Medication Adherence Rating Scale (MARS), and QoL was assessed using the WHO-QoL-BREF instrument. Data were analyzed using descriptive statistics and multiple regression to identify predictors of adherence and QoL. RESULTS: The study reports a mean age of 55.69 years, with a male preponderance (59.89%). Sixty-one per cent exhibited low adherence scores (MARS 0–5), with a mean adherence score of 6.98. Higher adherence was significantly associated with improved fasting plasma glucose and postprandial glucose levels, although HbA1c levels were similar across adherence groups. QoL scores were highest in the physical, psychological, and social domains for patients with better adherence. Multiple regression analysis identified adherence as an independent predictor of QoL (p < 0.05) after adjusting for sociodemographic and clinical variables. CONCLUSIONS: This study highlights the critical link between medication adherence and improved QoL in T2D patients. Interventions targeting adherence barriers, particularly in rural populations, can enhance glycemic outcomes and QoL, underscoring the importance of patient-centered strategies in diabetes care.

Mucosal involvement is nearly ubiquitous in paraquat poisoning. Initially, the tongue becomes erythematous and swollen, later developing erosions and ulcerations often covered with yellowish necrotic debris, termed as ‘Paraquat tongue’. Associated symptoms include severe pain, burning sensation, dysphagia and excessive salivation. Mucosal lesions in the pharynx, oesophagus and stomach are also common. The presence of the paraquat tongue should prompt clinicians to diligently assess for gastrointestinal perforation, mediastinitis, pneumothorax and pneumomediastinum.

Human brucellosis is a chronic systemic infection mostly presenting as afebrile illness with musculoskeletal complaints with organomegaly and diagnosis is based on serology. The diagnostic tests are sparsely available in India and even less prescribed. We report six cases of human of brucellosis presenting as fever with rheumatic manifestation along with their outcome.

Chemotherapy, radiotherapy and surgical treatments of cancer having several limitations and toxic side‐effects, have led researchers to focus towards development of alternative natural plant‐based therapeutics that can reduce disease severity. The present research work is mainly focussed towards identifying molecular mechanisms of apoptosis of colorectal cancer cells (HCT116) by perennial herb Bryophyllum pinnatum leaf‐extract via both in vitro experimentations and in silico analysis. B. pinnatum leaf extract induced highest cytotoxicity at lowest dose (IC 50 :0.01 mg/mL) against HCT116 cells with 49.5% ( p < 0.0001) cellular death, in comparison to other cancer cell lines. It has arrested HCT116 cell populations at G2/M cell‐cycle phase and led to 10 folds ( p < 0.0001) and 5.5 folds ( p < 0.0001) increased intracellular ROS production in treated groups. ROS production might have led to significant 34.23% and 21.03% ( p < 0.0001) apoptosis in treated cells, proved in vitro and in silico, with significant upregulation of p53 ( p < 0.0001), BAX ( p = 0.0252), CASPASE3 ( p < 0.0001) and downregulation of BCL2 ( p = 0.0058), leading to increased nuclear p53 ( p = 0.0002) accumulation in treated cells, suggesting that the leaf‐extract might have induced p53‐dependent apoptosis of colorectal cancer cells. The phyto‐extract also possess significant gene‐modulatory potential as evident from qRT‐PCR analysis of oncogenes and tumor suppressor genes. Leaf's bioactive phyto‐constituents were elucidated by GC‐MS and HPLC‐ESI/MS analysis. In silico STITCH analysis provided significant network interactions between these bioactive phyto‐compounds and studied proteins. Further Molecular Docking studies revealed strong binding between such docked complexes. Also, predicted major bioactive phyto‐constituents of B. pinnatum leaf‐extract such as Quercetin, Morin and β‐Sitosterol have induced significant ( p < 0.0001) apoptosis and increased intracellular ROS, validating their in silico interactions with studied proteins of HCT116 cells. All these studies together demonstrated ability of B. pinnatum to be used as a suitable natural phyto‐therapeutic agent for development of chemo‐preventive medications against colorectal cancer.

Background: Atopic dermatitis (AD) is a chronic relapsing inflammatory disease that impacts the quality of life of affected individuals as well as their families. Its pathogenesis involves impaired skin barrier function and immune dysregulation. Moisturizers are used in AD management as they help in repairing the skin barrier. Objective: The objective of this study was to compare the efficacy, safety, and prevention of relapse with ceramide-based post-biotic moisturizer against paraffin-based moisturizer in mild to moderate AD. Method: A total of 160 AD patients were grouped into two: Group I received desonide cream 0.05% and ceramide-based post-biotic moisturizer and Group II received desonide cream 0.05% and paraffin-based moisturizer. Both groups were given treatment for four weeks. Patients who achieved complete resolution entered the maintenance phase for a maximum duration of three months. They were followed up every two weeks telephonically or as and when the patient experienced a relapse. Results: All 160 patients were completely cured and entered the maintenance phase at week 4. A total of 96/160 (71.25%) patients relapsed, with 44 relapses in Group I (55%) and 52 (65%) in Group II (p=0.25). However, in terms of mean relapse time, Group I had a 72.52±15.01 day remission period, whereas Group II had a 47.44±21.49 day remission period (p=0.0001). Moreover, Group I showed a statistically significantly prolonged estimated median time to relapse compared with Group II (median: 85 days versus 71 days, p=0.05). Both moisturizers were tolerated very well. Conclusion: Although both moisturizers were effective in resolving symptoms in the treatment phase, the ceramide-based post-biotic moisturizer was more effective and statistically significant in extending the remission period against the paraffin-based moisturizer in patients with mild to moderate AD

Background Given the complex nature of type 2 diabetes (T2D), monotherapy often fails to maintain long-term glycemic control, when combination therapy using multiple medications with complementary mechanisms of action comes to the rescue. Among the various treatment options, dipeptidyl peptidase-4 (DPP-4) inhibitors like vildagliptin and newer agents like imeglimin have shown promise. Objective The present study evaluated and compared the safety and effectiveness of imeglimin and vildagliptin as add-on therapies in T2D Methods This retrospective cohort study included patients with HbA1c levels 7.5–8.5% at the time of initiating the add-on therapy (with either vildagliptin 100 mg (once daily) or imeglimin 1 gm (twice daily)) for at least 6 months. Demographic details, medical history, baseline and follow-up values glycemic, hepatic, and renal measures were noted, along with the incidence of reported adverse reactions. Results With comparable baseline metrics, the study showed a significant reduction in FPG by 34.51 mg/dL from baseline for the imeglimin group, as compared to 26.21 mg/dL for the vildagliptin group. A mean reduction of 46.31 mg/dL in PPPG was noted in the imeglimin group as compared to 29 mg/dL for the vildagliptin group. A reduction of 0.98% HbA1C was noted in imeglimin add-ons as compared to 0.59% in vildagliptin add-ons. A significant decrease in SGOT and SGPT was also noted. Comparable safety profile was noted for both groups with the incidence of ADRs being 5.71% and 4.58% for imeglimin and vildagliptin, respectively. Conclusion Imeglimin and vildagliptin are both effective and safe add-on therapies for managing T2DM. While imeglimin may offer some advantages in terms of β-cell preservation and insulin sensitivity, the choice between these two agents should be individualized based on patient characteristics, preferences, and clinical response.