Sotagliflozin

Sotagliflozin

Clinical data
Pronunciation	/ˌsoʊtəɡlɪˈfloʊzɪn/ SOH-tə-gli-FLOH-zin
Trade names	Zynquista, Inpefa
AHFS/Drugs.com	Monograph
MedlinePlus	a624022
License data	US  DailyMed:  Sotagliflozin
Routes of administration	By mouth
Drug class	SGLT2 inhibitor
ATC code	A10BK06 ( WHO )
Legal status
Legal status	US: ℞-only [1] EU:Rx-only [2]
Identifiers
CAS Number	1018899-04-1
PubChem CID	24831714
DrugBank	12713
ChemSpider	27289071
UNII	6B4ZBS263Y
KEGG	D10669
ChEBI	CHEBI:229226
CompTox Dashboard (EPA)	DTXSID20144314
ECHA InfoCard	100.231.837
Chemical and physical data
Formula	C21H25ClO5S
Molar mass	424.94 g·mol−1
3D model (JSmol)	Interactive image
SMILES CCOC1=CC=C(C=C1)CC2=C(C=CC(=C2)[C@H]3[C@@H]([C@H]([C@@H]([C@H](O3)SC)O)O)O)Cl
InChI InChI=1S/C21H25ClO5S/c1-3-26-15-7-4-12(5-8-15)10-14-11-13(6-9-16(14)22)20-18(24)17(23)19(25)21(27-20)28-2/h4-9,11,17-21,23-25H,3,10H2,1-2H3/t17-,18-,19+,20+,21-/m1/s1 Key:QKDRXGFQVGOQKS-CRSSMBPESA-N

Sotagliflozin, sold under the brand name Inpefa among others, is a medication used to reduce the risk of death due to heart failure. ^[1] It is an inhibitor of sodium-glucose cotransporter 1 and 2 (SGLT1/SGLT2 inhibitor). ^[1] It is taken by mouth. ^[1]

The most common adverse reactions inlude urinary tract infection, volume depletion, diarrhea, and hypoglycemia. ^[1]

Sotagliflozin was approved for medical use in the European Union in April 2019, as Zynquista, for the treatment for type 1 diabetes, ^[2] and in the United States in May 2023, ^[3] to reduce the risk of death due to heart failure. ^{[1] [4]} The marketing authorization for sotagliflozin was withdrawn in the EU in August 2022, at the request of the marketing-authorization holder. ^[2]

Medical uses

In the United States, sotagliflozin is indicated to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with heart failure; or type 2 diabetes, chronic kidney disease, and other cardiovascular risk factors. ^{[1] [3]}

Pharmacology

Sotaglifozin is a sodium-glucose co-transporter 1 and 2 inhibitor that reduces both postprandial glucose and insulin levels by delaying intestinal glucose absorption, decreases gastric inhibitory polypeptide, and elevations in glucagon-like peptide and peptide yy levels are consistent with local inhibition of intestinal SGLT1. ^[5]

History

The US Food and Drug Administration (FDA) approved sotagliflozin based on evidence from two clinical trials of 11,806 total participants with heart failure or with type 2 diabetes, chronic kidney disease, and other cardiovascular risk factors. ^[3] The trials were conducted at 322 sites in 32 countries (SOLOIST/NCT03521934 ^{[1] [6]} ) and 750 sites in 42 countries (SCORED/NCT03315143 ^{[1] [7]} ) primarily in Europe, South America, and North America. ^[3] Both trials were used for primary determination of the benefits and side effects of the drug. ^[3] The benefits and side effects of sotagliflozin were evaluated in the two clinical trials. ^[3] In both trials, participants were randomly assigned to receive either sotagliflozin or placebo by mouth once a day. ^[3] Neither the participants nor the healthcare providers knew which treatment was being given until after the trial was completed. ^[3] The benefit of sotagliflozin was evaluated by measuring the number of predefined events (death from cardiovascular causes, need for hospitalization for heart failure, or urgent medical care visit for heart failure) occurring in the patient population receiving sotagliflozin versus placebo. ^[3]

Society and culture

Legal status

The US Food and Drug Administration (FDA) refused its approval for use in combination with insulin for the treatment of type 1 diabetes. It is developed by Lexicon Pharmaceuticals. ^{[8] [9]}

In May 2023, the US FDA approved sotagliflozin (Inpefa) to decrease the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with heart failure or type 2 diabetes, chronic kidney disease, and other cardiovascular risk. ^{[3] [4]}

The marketing authorization for sotagliflozin was withdrawn in the EU in August 2022, at the request of the marketing-authorization holder. ^[2]

Research

Combination of insulin with sotaglifozin led to a significant lowering of systolic and diastolic blood pressure and multiple indirect markers of arterial stiffness, including pulse pressure, without changes in pulse rates. ^[10]

References

1. "Inpefa- sotagliflozin tablet". DailyMed. 5 June 2023. Archived from the original on 26 June 2023. Retrieved 25 June 2023.
2. "Zynquista EPAR". European Medicines Agency (EMA). 27 February 2019. Archived from the original on 3 November 2020. Retrieved 28 October 2020. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
3. "Drug Trials Snapshots: Inpefa". U.S. Food and Drug Administration (FDA). 26 May 2023. Retrieved 15 July 2024. This article incorporates text from this source, which is in the public domain .
4. "Lexicon Announces FDA Approval of Inpefa (sotagliflozin) for Treatment of Heart Failure" (Press release). Lexicon Pharmaceuticals. 26 May 2023. Archived from the original on 20 October 2023. Retrieved 28 May 2023– via GlobeNewswire.
5. Powell DR, Zambrowicz B, Morrow L, Beysen C, Hompesch M, Turner S, et al. (April 2020). "Sotagliflozin Decreases Postprandial Glucose and Insulin Concentrations by Delaying Intestinal Glucose Absorption". The Journal of Clinical Endocrinology and Metabolism. 105 (4): e1235 –e1249. doi: 10.1210/clinem/dgz258 . PMC   7067537 . PMID   31837264.
6. "Effect of Sotagliflozin on Cardiovascular Events in Participants With Type 2 Diabetes Post Worsening Heart Failure (SOLOIST-WHF Trial)". ClinicalTrials.gov. Retrieved 15 July 2024.
7. "Effect of Sotagliflozin on Cardiovascular and Renal Events in Participants With Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk (SCORED)". ClinicalTrials.gov. Retrieved 15 July 2024.
8. "Sotagliflozin as an Adjunct to Insulin for Type 1 Diabetes" (PDF). U.S. Food and Drug Administration (FDA). 17 January 2019. Archived from the original (PDF) on 26 April 2019.
9. "Sanofi: FDA advisory committee votes on Zynquista (sotagliflozin) as treatment for adults with type 1 diabetes" (Press release). Sanofi. 17 January 2019. Archived from the original on 1 August 2019. Retrieved 1 April 2019– via GlobeNewswire.
10. Rodbard HW, Giaccari A, Cariou B, Garg S, Davies MJ, Seth K, et al. (2021). "Effect of sotagliflozin as an adjunct to insulin therapy on blood pressure and arterial stiffness in adults with type 1 diabetes: A post hoc pooled analysis of inTandem1 and inTandem2". Diabetes & Vascular Disease Research. 18 (1): 1479164121995928. doi: 10.1177/1479164121995928 . PMC   8481733 . PMID   33611925.

Further reading

• Bhatt DL, Szarek M, Pitt B, Cannon CP, Leiter LA, McGuire DK, et al. (January 2021). "Sotagliflozin in Patients with Diabetes and Chronic Kidney Disease". The New England Journal of Medicine. 384 (2): 129–139. doi: 10.1056/NEJMoa2030186 . PMID   33200891.
• Cefalo CM, Cinti F, Moffa S, Impronta F, Sorice GP, Mezza T, et al. (February 2019). "Sotagliflozin, the first dual SGLT inhibitor: current outlook and perspectives". Cardiovascular Diabetology. 18 (1): 20. doi: 10.1186/s12933-019-0828-y . PMC   6393994 . PMID   30819210.
• Lapuerta P, Zambrowicz B, Strumph P, Sands A (March 2015). "Development of sotagliflozin, a dual sodium-dependent glucose transporter 1/2 inhibitor". Diabetes & Vascular Disease Research. 12 (2): 101–110. doi: 10.1177/1479164114563304 . PMID   25690134. S2CID   35513842.
• Szarek M, Bhatt DL, Steg PG, Cannon CP, Leiter LA, McGuire DK, et al. (August 2021). "Effect of Sotagliflozin on Total Hospitalizations in Patients With Type 2 Diabetes and Worsening Heart Failure : A Randomized Trial" (PDF). Annals of Internal Medicine. 174 (8): 1065–1072. doi:10.7326/M21-0651. hdl: 10138/340512 . PMID   34152828. S2CID   235596703.