A Study of Adverse Drug Reactions due to Anti-Obesity Drugs in Diabetic Patients in a Multispecialty Hospital

Abstract

Adverse drug reactions (ADRs) remain an important determinant of patient safety and therapeutic success, particularly in chronic diseases requiring long-term pharmacotherapy. The present study aimed to evaluate ADRs associated with anti-obesity drugs among diabetic patients in a multispecialty hospital. This open, non-comparative, observational study was carried out to monitor ADRs related to anti-obesity medications such as orlistat, liraglutide, and phentermine-topiramate combinations. A total of 268 ADRs were observed among 540 diabetic obese patients between 2021–2023. The majority of ADRs were mild (54.8%), followed by moderate (36.9%) and severe (8.2%). Gastrointestinal disturbances were the most frequently reported ADRs (43.2%), followed by injection site reactions (12.6%), headache (10.8%), insomnia (7.4%), and fatigue (6.7%). Combination therapy was associated with a lower overall incidence of ADRs compared to monotherapy. The findings emphasize the need for continuous pharmacovigilance and careful selection of anti-obesity therapy in diabetic patients to ensure optimal therapeutic outcomes and adherence.

Keywords

Introduction

Obesity and type 2 diabetes mellitus (T2DM) are intricately linked metabolic disorders that have reached epidemic proportions globally. Their coexistence not only exacerbates individual disease burden but also significantly elevates the risk of cardiovascular complications, dyslipidemia, insulin resistance, and other chronic conditions. The pathophysiological overlap between these disorders—characterized by impaired glucose metabolism, systemic inflammation, and hormonal dysregulation—creates a synergistic effect that accelerates disease progression and increases healthcare costs.Weight management is a cornerstone of diabetes care. Clinical evidence consistently demonstrates that intentional weight reduction in patients with T2DM leads to substantial improvements in glycemic control, blood pressure regulation, lipid profiles, and overall metabolic health. These benefits translate into reduced long-term morbidity and mortality, making weight loss a critical therapeutic target in this population.While lifestyle interventions such as dietary modification, physical activity, and behavioral therapy remain first-line strategies, their effectiveness is often limited by poor adherence, psychological barriers, and the complex interplay of metabolic factors. Consequently, pharmacological therapy is recommended when non-pharmacologic approaches fail to achieve clinically meaningful weight loss. Several anti-obesity agents have been approved for use, including orlistat (a gastrointestinal lipase inhibitor), liraglutide (a glucagon-like peptide-1 receptor agonist), naltrexone-bupropion (a combination targeting reward and appetite pathways), and phentermine-topiramate (a sympathomimetic-anticonvulsant combination). These drugs offer varying degrees of efficacy in weight reduction and metabolic improvement, and some have demonstrated additional benefits such as appetite suppression, improved insulin sensitivity, and cardiovascular risk reduction. However, the use of anti-obesity pharmacotherapy is not without challenges. Adverse drug reactions (ADRs) are frequently reported and may range from mild gastrointestinal discomfort to severe neuropsychiatric and metabolic disturbances. These reactions can negatively impact patient adherence, compromise therapeutic outcomes, and necessitate discontinuation or modification of treatment. According to the World Health Organization (WHO), an ADR is defined as “a response to a drug that is noxious and unintended and occurs at doses normally used in humans.” Post-marketing surveillance and clinical reports have identified a spectrum of ADRs associated with anti-obesity agents, including steatorrhea, bloating, injection site reactions, insomnia, anxiety, hypoglycemia, and pancreatitis.

Despite the increasing prescription of these agents among diabetic patients, there remains a paucity of data specifically addressing their safety profile in this high-risk population. Diabetic individuals are particularly vulnerable to ADRs due to polypharmacy, altered pharmacokinetics, comorbid conditions, and organ dysfunction. Understanding the pattern, frequency, and severity of ADRs in this group is essential for informed prescribing, risk mitigation, and patient education.

Therefore, the present study was undertaken to systematically evaluate the ADR profile of anti-obesity drugs in patients with diabetes mellitus. The objectives were to characterize the types of ADRs encountered, assess their severity and causality, and identify patient-specific risk factors contributing to adverse outcomes. Emphasis was placed on pharmacovigilance practices and clinical safety monitoring to support evidence-based decision-making and enhance the therapeutic safety of anti-obesity pharmacotherapy in diabetic care.

MATERIALS AND METHODS

An open, non-comparative, observational study was conducted between January 2021 and December 2023 in a multispecialty tertiary care hospital. Ethical clearance was obtained from the institutional review board prior to initiation.
Adult diabetic patients (age 30–75 years) who were prescribed anti-obesity medications were included. Patients with psychiatric disorders, hepatic or renal failure, or those on investigational drugs were excluded. Written informed consent was obtained from all participants.
Data regarding demographics, medication history, and observed ADRs were collected during routine follow-up visits. ADRs were assessed using the WHO–Uppsala Monitoring Centre (UMC) Causality Assessment Scale, and their severity was graded according to Hartwig’s Severity Assessment Scale. Statistical analysis was performed using GraphPad Prism (version 8.0); p<0.05 was considered significant.

RESULTS

A total of 540 diabetic obese patients were enrolled (280 females, 260 males). The mean age was 55.8 ± 10.7 years, and mean BMI was 33.4 ± 3.9 kg/m².

A total of 268 ADRs were reported. Females experienced a slightly higher number of ADRs (55.6%) compared to males (44.4%).

Severity of ADRs

Type of ADRs

Drug-wise Distribution of ADRs

Monotherapy vs Combination Therapy

Combination therapy (anti-obesity drug + metformin) exhibited a lower ADR incidence (41.7%) compared to monotherapy (58.3%).

Causality Assessment (WHO-UMC Scale)

Combination therapy (anti-obesity + metformin) showed lower ADR incidence (41.7%) than monotherapy (58.3%).

DISCUSSION

This study delineates the adverse drug reaction (ADR) profile of anti-obesity agents in patients with diabetes—a population uniquely susceptible due to the interplay of polypharmacy, metabolic dysregulation, and comorbid conditions. The overall incidence of ADRs was moderate and consistent with data from prior post-marketing surveillance studies, reinforcing the need for continued real-world safety evaluations.

Gastrointestinal ADRs emerged as the most frequently reported, particularly among patients receiving orlistat. This is attributable to its pharmacodynamic mechanism of inhibiting fat absorption, which commonly results in steatorrhea, bloating, and other digestive disturbances. Liraglutide users experienced injection site reactions, while neuropsychiatric symptoms such as insomnia and anxiety were more prevalent in those treated with phentermine-topiramate—highlighting the drug-specific nature of ADR manifestations.

Importantly, the majority of ADRs were classified as mild to moderate in severity, suggesting that these events were largely manageable through dose titration, patient counselling, and supportive care. However, a subset of patients (8.2%) experienced severe ADRs, including recurrent hypoglycemia and acute pancreatitis, particularly in association with liraglutide. These findings underscore the necessity for rigorous clinical monitoring, especially in individuals with complex metabolic profiles or compromised organ function.

A notable observation was the predominance of ADRs among female patients, which aligns with global pharmacovigilance data. This trend may be influenced by sex-specific hormonal factors, differential pharmacokinetics, and heightened reporting behavior. The WHO causality assessment revealed that 55% of ADRs were deemed probable or certain, indicating a strong temporal association between drug exposure and reaction onset and reinforcing the clinical relevance of these findings.

Collectively, these insights emphasize the importance of individualized therapy, proactive ADR surveillance, and patient education in optimizing the safety and efficacy of anti-obesity pharmacotherapy in diabetic populations. Future studies should aim to stratify risk based on genetic, behavioral, and pharmacological variables to further refine treatment algorithms and minimize adverse outcomes.

CONCLUSION

This study affirms that anti-obesity pharmacotherapy is generally well tolerated in patients with diabetes, reinforcing its role as a valuable adjunct in comprehensive metabolic management. Despite favourable tolerability profiles, gastrointestinal and neuropsychiatric adverse drug reactions (ADRs) remain the most prevalent, underscoring the need for ongoing vigilance in clinical practice.

To mitigate these risks and enhance therapeutic adherence, a multidimensional strategy is imperative. Continuous pharmacovigilance should be prioritized to detect and address emerging safety signals promptly. Individualized treatment regimens—based on patient-specific factors such as glycemic control, comorbidities, organ function, and psychosocial context—can significantly improve outcomes and minimize adverse events. Furthermore, structured patient education initiatives are essential to foster informed decision-making, promote adherence, and enable early recognition of ADRs.

Clinicians are advised to conduct comprehensive pre-treatment evaluations, including assessments of hepatic and renal function, screening for potential drug–drug interactions, and identifying risk factors such as age, mental health status, and polypharmacy. Integrating shared decision-making and evidence-based guidance into routine care can strengthen the therapeutic alliance and ensure that pharmacological interventions align with both clinical goals and patient preferences.

In conclusion, while anti-obesity agents offer substantial benefits in the diabetic population, their safe and effective use demands a personalized, vigilant, and patient-centered approach. Future research should continue to explore long-term safety profiles and real-world effectiveness to further inform clinical guidelines and optimize care delivery.

REFERENCES

1. WHO. The use of the WHO–UMC system for standardized case causality assessment. Uppsala Monitoring Centre; 2021.
2. Astrup A, et al. Safety and tolerability of anti-obesity medications: A review of clinical data. Int J Obes (Lond). 2021;45(4):923–937.
3. Pi-Sunyer X. Pharmacotherapy for obesity in type 2 diabetes: Current perspectives. Diabetes Care. 2022;45(8):1801–1809.
4. Bray GA, Ryan DH. Medical therapy for the patient with obesity. N Engl J Med. 2021;384(10):989–1002.
5. Gadde KM, et al. Combination pharmacotherapy for obesity. J Clin Endocrinol Metab. 2020;105(6):dgaa101.
6. Nauck MA, Meier JJ. Incretin-based therapies: Safety and efficacy in diabetes and obesity. Diabetes Obes Metab. 2021;23(S1):5–16.
7. Kang JG, Park CY. Anti-obesity drugs: A review about their effects and safety. Diabetes Metab J. 2020;44(6):802–818.
8. Padwal RS, et al. Long-term efficacy and safety of anti-obesity drugs. Obes Rev. 2019;20(7):931–944.
9. Apovian CM. Pharmacologic management of obesity: An Endocrine Society guideline. J Clin Endocrinol Metab. 2015;100(2):342–362.
10. Chitturi S, Farrell GC. Drug-induced liver disease: Mechanisms and management. J Gastroenterol Hepatol. 2021;36(4):792–805.
11. Wadden TA, Bailey TS, Billings LK, et al. Effect of subcutaneous semaglutide vs placebo as adjunct to intensive behavioral therapy on body weight in adults with overweight or obesity. JAMA. 2021;325(14):1403–1413.
12. Wilding JPH, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384:989–1002.
13. Jensen MD, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults. Circulation. 2014;129(25 Suppl 2):S102–S138.
14. Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: A systematic and clinical review. JAMA. 2014;311(1):74–86.
15. James WPT, et al. Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N Engl J Med. 2010;363(10):905–917.
16. Kushner RF, Kahan S. Introduction: The state of obesity in 2023. Med Clin North Am. 2023;107(1):1–12.
17. Greenway FL. Physiological adaptations to weight loss and factors favouring weight regain. Int J Obes (Lond). 2015;39(8):1188–1196.
18. Piaggi P, Thearle MS, Krakoff J. Genetic determinants of weight gain in response to obesity treatment. Diabetes. 2021;70(5):1100–1110.
19. Verhaegen AA, Van Gaal LF. Drug-induced obesity and its treatment. Endocrinol Metab Clin North Am. 2020;49(2):223–235.
20. George A, Jacob S, Abraham S, et al. Pharmacovigilance of anti-obesity drugs: An Indian perspective. Indian J Pharmacol. 2022;54(2):103–111.
21. Dutta D, Mukhopadhyay S. Safety concerns with anti-obesity pharmacotherapy in patients with diabetes mellitus. Curr Diabetes Rev. 2020;16(5):401–414.
22. Wilding JPH, Batterham RL, Calanna S, et al. Long-term safety and efficacy of liraglutide in patients with obesity and type 2 diabetes. Lancet Diabetes Endocrinol. 2020;8(9):738–749.
23. Polyzos SA, Mantzoros CS. Obesity pharmacotherapy in clinical practice: A comprehensive, evidence-based review. Metabolism. 2021;123:154839.
24. Filippatos TD, Tsimihodimos V. Adverse effects of anti-obesity drugs on metabolic parameters: A clinical overview. Curr Pharm Des. 2019;25(33):3557–3564.
25. World Health Organization. Global report on diabetes. Geneva: WHO; 2023.