Saroglitazar (INN, trade name Lipaglyn) is a drug for the treatment of type 2 diabetes mellitus, dyslipidemia, NASH and NAFLD It is approved for use in India by the Drug Controller General of India.[1] Saroglitazar is indicated for the treatment of diabetic dyslipidemia and hypertriglyceridemia with type 2 diabetes mellitus not controlled by statin therapy. In clinical studies, saroglitazar has demonstrated reduction of triglycerides (TG), LDL cholesterol, VLDL cholesterol, non-HDL cholesterol and an increase in HDL cholesterol a characteristic hallmark of atherogenic diabetic dyslipidemia (ADD). It has also shown anti-diabetic medication properties by reducing the fasting plasma glucose and HBA1c in diabetes patients.
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| Trade names | Lipaglyn |
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| Routes of administration | Oral |
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| Formula | C25H29NO4S |
| Molar mass | 439.57 g·mol−1 |
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Mechanism of action
editSaroglitazar is an insulin sensitizer. It is a first in class drug which acts as a dual PPAR agonist at the subtypes α (alpha) and γ (gamma) of the peroxisome proliferator-activated receptor (PPAR). Agonist action on PPARα lowers high blood triglycerides, and agonist action on PPARγ improves insulin resistance and consequently lowers blood sugar.[2]
Efficacy
editBeing a dual PPAR agonist, saroglitazar helps in controlling blood glucose and lipid parameters, especially high triglycerides and high non-HDL cholesterol.[3][4][5] A study done in rats concluded that saroglitazar has the potential to prevent the progression of retinopathy in diabetes patients.[6] Using preclinical models, it has also been shown to be useful in diabetic nephropathy.[7]
Safety
editNo major serious adverse events have been reported; however, long-term cardiovascular safety has not been established.[8] Concerns have been raised regarding increase in serum creatinine with the use of saroglitazar, initially noted in a meta-analysis published by Dutta et. al. [9] In another randomized controlled trial published by Gawrieh et. al., a mild but significant increase in serum creatinine was noted with 16 weeks use of saroglitazar at 4mg/day dose. [10]
Controversies
editIn December 2016, Zydus Discovery DMCC, a research subsidiary Zydus Lifesciences, was cited by the US FDA for deliberately misbranding saroglitazar. In a December 21, 2016, letter to the company, the US FDA asked it to stop using broad statements, such as the "world's first" and to stop suggesting that the drug is approved throughout the world, including in the United States, when that is not true. [11]
References
edit- ^ Ramalingam A (6 June 2013). "Zydus Group launches new diabetic drug". The Times of India.
- ^ "Lipaglyn (Saroglitazar) for Treating Hypertriglycerdemia in Type II Diabetes, India". Drug Development and Technology. Archived from the original on 12 May 2014.
- ^ Manoria PC, Chopra HK, Parashar SK, Dutta AL, Pinto B, Mullasari A, Prajapati S (December 2013). "The nuances of atherogenic dyslipidemia in diabetes: focus on triglycerides and current management strategies". Indian Heart Journal. 65 (6): 683–690. doi:10.1016/j.ihj.2013.10.015. PMC 3905264. PMID 24407538.
- ^ Chatterjee S, Majumder A, Ray S (January 2015). "Observational study of effects of Saroglitazar on glycaemic and lipid parameters on Indian patients with type 2 diabetes". Scientific Reports. 5: 7706. Bibcode:2015NatSR...5E7706C. doi:10.1038/srep07706. PMC 4287720. PMID 25573251.
- ^ Ramakrishnan S (2015). "From 'Make in India' to 'Made in India': the saroglitazar story". Indian Heart Journal. 67 (1): 8–10. doi:10.1016/j.ihj.2015.02.014. PMC 4382552. PMID 25820041.
- ^ Joharapurkar A, Patel V, Kshirsagar S, Patel MS, Savsani H, Jain M (May 2021). "Effect of dual PPAR-α/γ agonist saroglitazar on diabetic retinopathy and oxygen-induced retinopathy". European Journal of Pharmacology. 899: 174032. doi:10.1016/j.ejphar.2021.174032. PMID 33753107. S2CID 232326306.
- ^ WO 2017089979, Jain M, Joharapurkar A, Kshirsagar S, "Dual PPAR modulators for the treatment of diabetic nephropathy and related diseases", published 1 June 2017, assigned to Cadila Healthcare Limited
- ^ Munigoti SP, Harinarayan CV (May 2014). "Role of Glitazars in atherogenic dyslipidemia and diabetes: Two birds with one stone?". Indian Journal of Endocrinology and Metabolism. 18 (3): 283–287. doi:10.4103/2230-8210.131134. PMC 4056123. PMID 24944919.
- ^ Dutta D, Bhattacharya S, Surana V, Aggarwal S, Singla R, Khandelwal D, Sharma M (Nov–Dec 2020). "Efficacy and safety of saroglitazar in managing hypertriglyceridemia in type-2 diabetes: A meta-analysis". Diabetes & Metabolic Syndrome. 14 (6): 1759–1768. doi:10.1016/j.dsx.2020.08.039. PMID 32937280. S2CID 221767590.
- ^ Gawrieh S, Noureddin M, Loo N, Mohseni R, Awasty V, Cusi K, et al. (October 2021). "Saroglitazar, a PPAR-α/γ Agonist, for Treatment of NAFLD: A Randomized Controlled Double-Blind Phase 2 Trial". Hepatology. 74 (4): 1809–1824. doi:10.1002/hep.31843. hdl:1805/26913. PMID 33811367. S2CID 232772287.
- ^ Dandekar V (28 December 2016). "Cadila Healthcare misbranded Saroglitazar, says US FDA". The Economic Times.