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Sulfonylureas and Cardiovascular Mortality? 559

increased risk ofmyocardial infarction (OR 0.92 [95% 4. Abdelmoneim AS, Eurich DT, Light PE, Senior PA, Seubert JM, Makowsky
CI 0.76 to 1.12]) or stroke (OR 1.16[95% CI 0.81 to 1.66]). 7 MJ, Simpson SH. Cardiovascular safety of sulfonylureas: over 40 years of
continuous controversy without an answer. Diabetes ObesMetab. 2015
Jun;17(6):523-32.
Summary
5. Kumar R, Kerins DM, Walther T. Cardiovascular safety of anti-diabetic
Diabetes is a worldwide epidemic metabolic disorder drugs. Eur Heart J Cardiovasc Pharmacother. 2016 Jan;2(1):32-43.
and many Indians are diabetic or at risk of diabetes. 6. Kalra S, Aamir AH, Raza A, Das AK, Azad Khan AK, Shrestha D, et al.
Although, newer drugs are being introduced as better Place of sulfonylureas in the management of type 2 diabetes mellitus
drugs for glycemic control, sulfonylureas have long in South Asia: A consensus statement. Indian J Endocrinol Metab. 2015
proven to be effective and safe for over 50 years. Sep-Oct;19(5):577-96.
There is a causal relationship between sulfonylureas 7. VarvakiRados D, Catani Pinto L, ReckRemonti L, BauermannLeitão C,
and adverse cardiovascular events based on the bio- Gross JL. The Association between Sulfonylurea Use and All-Cause and
logically plausible mechanisms; however, the majori- Cardiovascular Mortality: A Meta-Analysis with Trial Sequential Analysis
of Randomized Clinical Trials. PLoS Med. 2016 Apr 12;13(4):e1001992.
ty of this is based on animal studies. Evidence from
RCTs suggest a neutral effect between sulfonylureas 8. Highlighting points
and adverse cardiovascular outcomes, whereas evi- 9. Sulfonylureasare considered to be one of the leading oral hypoglycaemic
dence from observational studies suggests increased agents over the past half century.
cardiovascular risk with sulfonylureas.Furthermore, it 10. There is a controversy about cardiovascular safety of sulfonylureas.
may not be a group effect as it is not observed with 11. Sulfonylureas may cause cardiovascular adverse effects by inhibiting ex-
second and third generation Sulfonylureas.Clinicians tra-pancreatic KATP channelsand sulphonylurea receptors present in abun-
should consider possible differences in risk of mor- dance in cardiacmyocytesand smooth muscle cells.
tality when selecting a sulfonylurea. 12. Results of meta-analysis of RCTs suggest no increased risk of cardiovascular
adverse effects with newer sulfonylureas.
Highlighting points 13. Results of meta-analysis of observational studies indicate increased risk of
• Sulfonylureasare considered to be one of the cardiovascular adverse effectswith the older sulfonylureas.
leading oral hypoglycaemic agents over the past 14. Differences between different generation of sulfonylureas indicate that
half century. adverseeffect on cardiovascular system may not be a group effect.
• There is a controversy about cardiovascular safety
of sulfonylureas.

• Sulfonylureas may cause cardiovascular adverse
effects by inhibiting extra-pancreatic KATP chan-
nelsand sulphonylurea receptors present in abun-
dance in cardiacmyocytesand smooth muscle
cells.
• Results of meta-analysis of RCTs suggest no in-
creased risk of cardiovascular adverse effects with
newer sulfonylureas.
• Results of meta-analysis of observational studies
indicate increased risk of cardiovascular adverse
effectswith the older sulfonylureas.
• Differences between different generation of sulfo-
nylureas indicate that adverseeffect on cardiovas-
cular system may not be a group effect.

Reference
1. Kaveeshwar SA, Cornwall J. The current state of diabetes mellitus in India.
Australas Med J. 2014;7(1):45-8.
2. IDF. Treatment algorithm for people with type 2 diabetes. Available at
http://www.idf.org/treatment-algorithm-people-type-2-diabetes. Accessed
on 20August 2017
3. Standards of Medical Care in Diabetes—2016, Diabetes Care.
2016;39(Suppl 1): S1-112.

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