GLP-1RA for glycaemic control and obesity as add on therapy for type 2 diabetes
Samia A. Elmiladi
Abstract: Diabetes mellitus (DM) is a complex and chronic illness requiring continuous medical care. Type 2 diabetes (T2D) is commonly associated with obesity, hypertension, and a tendency to develop thrombosis, and increase risk of cardiovascular diseases (CVD). Diabesity is a term used to indicate an coexistence of obesity and DM. Diabesity increases as obesity is an emerging epidemic of modern societies, the co-incidence with DM is also rising, so a joint plan of anti-obesity and anti-hyperglycemia for the management approaches. Therefore, this study aimed to identify the impact of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on bodyweight and glycemic response in obese Libyan patients with T2D at the National Diabetes Centre in Tripoli, between July 2013 and May 2022. This prospective study included obese adults with T2D who were newly prescribed GLP-1RA therapy for six months with dulaglutide once weekly or liraglutide once daily. The study included 170 diabetic patients were started on GLP1-RA as add on therapy to their treatment, with a regular follow up with dietitian and their physicians to adjusted their glucose lowering medications, than comparing the effect of these agents on bodyweight and the level of glycated hemoglobin before and after 24 weeks of treatment. Most of the patients (n = 99, 58.23%) were in the age period from 54 to 74 years old and 101 of whom were female subjects (59.4%), with a mean duration of DM equal to 8.8 ± 7.3 years. The patients were divided randomly into two groups, the first group included 110 patients who received liraglutide pens showed a significantly reduction in HbA1c from 9.6% (± 1.54) to 7.4% (± 1.03) by p < 0.001 and a significantly weight loss from 88.3 kg (± 10.68) to 80.8 kg (± 11.83) by p < 0.001. The reported adverse events were in 23 cases of minor hypoglycemia due to gastrointestinal upset. The other group included 60 patients for dulaglutide pens showed a significant decrease in HbA1c = 9.6% (± 1.54) to 7.1% (± 1.2) by p < 0.05 and a significant reduction of bodyweight from 88.3 kg (± 10.68) to 83.8 kg (± 16.3) by p < 0.05. The reported adverse events were mild transient gastrointestinal distressed for initial week of start than subside with regular intake. Whereas, 115 patients (67.6%) with HbA1c above 10.0% before start therapy, no patient with HbA1c above 10.0% after six months of both GLP-RA agents therapy. Thus, uses of GLP-RA as add on therapy for obese patients with T2D significantly improved the glycaemic control with less hypoglycaemia, accordingly, reduce insulin requirement for the blood glucose control and loss in bodyweight. It can thus be concluded that GLP-1RA therapy is an effective treatment option when used in the obese patients with DM.
1. Frühbeck G, Toplak H, Woodward E, Yumuk V, Maislos M, Oppert J-M, Executive Committee of the European Association for the Study of Obesity (2013) Obesity: the gateway to ill health - an EASO position statement on a rising public health, clinical and scientific challenge in Europe. Obesity Facts. 6 92): 117-120. doi: 10.1159/ 000350627.
2. Kelly T, Yang W, Chen CS, Reynolds K, He J (2008) Global burden of obesity in 2005 and projections to 2030. International Journal of Obesity. 32 (9): 1431-1437. doi: 10.1038/ijo.2008.102.
3. Dyson PA (2010) The therapeutics of lifestyle management on obesity. Diabetes, Obesity and Metabolism. 12 (11): 941-946. doi: 10.1111/j.1463-1326.2010.01256.x.
4. Oldridge NB, Stump TE, Nothwehr FK, Clark DO (2001) Prevalence and outcomes of comorbid metabolic and cardiovascular conditions in middle- and older-age adults. Journal of Clinical Epidemiology. 54 (9): 928-934. doi: 10.1016/s0895-4356(01)00350-x.
5. World Health Organization (2021) Obesity and overweight. 7/5/2022, WHO. Int. fact sheet. 9 June 2021.
6. Leitner DR, Frühbeck G, Yumuk V, Schindler K, Micic D, Woodward E, Toplak H (2017) Obesity and type 2 diabetes: two diseases with a need for combined treatment strategies - EASO can lead the way. Obesity Facts. 10 (5): 483-492. doi: 10.1159/000480525.
7. The Look AHEAD Research Group (2006) The Look AHEAD study: a description of the lifestyle intervention and the evidence supporting it. Obesity. 14 (5): 737-752. doi: 10.1038/oby.2006.84.
8. Ko JH, Kim TN (2022) Type 2 diabetes remission with significant weight loss: definition and evidence-based interventions. Journal of Obesity and Metabolic Syndrome. 31 (2): 123-133. doi: 10.7570/jomes22001.
9. Wing RR, Lang W, Wadden TA, Safford M, Knowler WC, Bertoni AG, Hill JO, Brancati FL, Peters A, Wagenknecht L (2011) Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes. Diabetes Care. 34 (7): 1481-1486. doi: 10.2337/dc10-2415.
10. Foster GD, Borradaile KE, Sanders MH, Millman R, Zammit G, Newman AB, Waddan TA, Kelley D, Wing RR, Pi-Sunyer FX, Reboussin D, Kuna ST (2009) A randomized study on the effect of weight loss on obstructive sleep apnea among obese patients with type 2 diabetes: the Sleep AHEAD study. Archives of Internal Medicine. 169 (17): 1619-1626. doi: 10.1001/ archinternmed.2009.266.
11. Rubin RR, Wadden TA, Bahnson JL, Blackburn GL, Brancati FL, Bray GA, Coday M, Crow SJ, Curtis JM, Dutton G, Egan C, Evans M, Ewing L, Faulconbridge L, Foreyt J, Gaussoin SA, Gregg EW, Hazuda HP, Hill JO, Horton ES, Hubbard VS, Jakicic JM, Jeffery RW, Johnson KC, Kahn SE, Knowler WC, Lang W, Lewis CE, Montez MG, Murillo A, Nathan DM, Patricio J, Peters A, Pi-Sunyer X, Pownall H, Rejeski WJ, Rosenthal RH, Ruelas V, Toledo K, Van Dorsten B, Vitolins M, Williamson D, Wing RR, Yanovski SZ, Zhang P (2014) Impact of intensive lifestyle intervention on depression and health-related quality of life in type 2 diabetes: the Look AHEAD Trial. Diabetes Care. 37 (6): 1544-1553. doi: 10.2337/dc13-1928.
12. Van Gaal L, Scheen A (2015) Weight management in type 2 diabetes: current and emerging approaches to treatment. Diabetes Care. 38 (6): 1161-1172. doi: 10.2337/dc14-1630.
13. Holst JJ, Deacon CF (2005) Glucagon-like peptide-1 mediates the therapeutic actions of DPP-IV inhibitors. Diabetologia. 48 (4): 612-615. doi.org/10.1007/s00125-005-1705-7.
14. Agius R, Coelho C, McGowan B (2022) GLP-1 analogues in clinical management of obesity. Current Opinion in Endocrine and Metabolic Research. 25: 100360. doi.org/10.1016/j.coemr.2022.100360.
15. American Diabetes Association (2021) 9. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2021. Diabetes Care. 44 (Suppl 1): S111-S124. doi: 10.2337/dc21-S009.
16. Pratley RE, Aroda VR, Lingvay I, Lüdemann J, Andreassen C, Navarria A, Viljoen A (2018) Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. Lancet Diabetes and Endocrinology. 6 (4): 275-286. doi: 10.1016/S2213-8587(18)30024-X.
17. Davies MJ, Bergenstal R, Bode B, Kushner RF, Lewin A, Skjøth TV, Andreasen AH, Jensen CB, DeFronze R (2015) Efficacy of liraglutide for weight loss among patients with type 2 diabetes: the SCALE diabetes randomized clini¬cal trial. Journal of the American Medical Association. 314 (7): 687-699. doi: 10.1001/jama.2015.9676.
18. Buse JB, Nauck M, Forst NT, Sheu WH-H, Shenouda SK, Heilmann CR, Hoogwerf BJ, Gao A, Boardman MK, Fineman M, Porter L, Schernthaner G (2013) Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a randomised, open-label study. Lancet. 381 (9861): 117-124. doi: 10.1016/ S0140-6736(12)61267-7.
19. Alruwaili H, Dehestani B, le Roux CW (2021) Clinical impact of liraglutide as a treatment of obesity. Clinical Pharmacology: Advances and Applications. 13: 53-60. doi: 10.2147/CPAA.S276085.
20. Elmiladi SA (2022) Presentation and character for adult patients with diabetes in Libya. Mediterranean Journal of Pharmacy and Pharmaceutical Sciences. 2 (1): 83 - 90. doi.org/10.5281/zenodo.6399891.
21. Zinman B, Nauck MA, Traberg HB, Larsen HF, Ørsted DD, Buse JB (2018) Liraglutide and glycaemic outcomes in the LEADER Trial. Diabetes Therapy: research, treatment and education of diabetes, and related disorders. 9 (6): 2383-2392. doi: 10.1007/s13300-018-0524-z.
22. Kaur P, Mahendru S, Mithal A (2016) Long-term efficacy of liraglutide in Indian patients with type 2 diabetes in a real-world setting. Indian Journal of Endocrinology and Metabolism. 20 (5): 595-599. doi: 10.4103/2230-8210. 183825.
23. Ostawal A, Mocevic E, Kragh N, Xu W (2016) Clinical effectiveness of liraglutide in type 2 diabetes treatment in the real-world setting: A systematic literature review. Diabetes Therapy: research, treatment and education of diabetes and related disorders. 7 (3): 411-438. doi: 10.1007/s13300-016-0180-0.
24. Jendle J, Grunberger G, Blevins T, Giorgino F (2016) Efficacy and safety of dulaglutide in the treatment of type 2 diabetes: a comprehensive review of the dulaglutide clinical data focusing on the AWARD phase 3 clinical trial program. Diabetes/Metabolism Research and Reviews. 32 (8): 776-790. doi: 10.1002/dmrr.2810.
Elmiladi SA (2023) GLP-1RA for glycaemic control and obesity as add on therapy for type 2 diabetes. Mediterr J Pharm Pharm Sci. 3 (2): 45-50. https://doi.org/10.5281/zenodo.7942952.