Saturday, December 21, 2024 12/21/2024

SGLT2 Inhibitors, Ketogenesis, and Ketoacidosis

Award Number: R01DK024092
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY/ABSTRACT Sodium-glucose cotransport inhibitors (SGLT2i) lower the plasma glucose concentration by promoting glucosuria and have been shown to be effective in preventing cardiovascular events, including heart failure, and in slowing the progression of chronic kidney disease in diabetic and nondiabetic individuals. However, the uptake of the SGLT2i, especially in the general medical community but also by cardiologists and nephrologists, has been retarded by the development of diabetic ketoacidosis. Although uncommon in T2DM, DKA occurs in 3-5% of T1DM individuals treated with SGLT2i and primarily for this reason the SGLT2i have not been approved by FDA for use in T1DM individuals. Consequently, T1DM subjects have been excluded from all large-scale CV and renal outcome studies. Further, the glucose lowering efficacy of the SGLT2i is blunted by their stimulation of hepatic glucose production (HGP), which offsets by ~50% the amount of glucose excreted in the urine. Therefore, a clearer understanding of the mechanisms involved in the stimulation of ketosis and EGP are needed. In the present grant proposal, we will employ innovative study designs with radioisotopes and stable isotopes to elucidate the mechanisms via which empagliflozin augments hepatic glucose production and stimulates ketogenesis (Protocols I, II, and III), while in Protocols IV and V we will examine whether pioglitazone can block the SGLT2i-induced stimulation of ketosis and HGP. If this can be demonstrated, this would allow T1DM, as well as T2DM, subjects to be safely treated with SGLT2i and to receive the cardiovascular and renal benefits of this antidiabetic class of drugs.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $647,274 )
2024	2024	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	39	7/12/2024	NON-COMPETING CONTINUATION	$647,274
														Subtotal = $647,274

Issue Date FY: 2023 ( Subtotal = $659,788 )
2023	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	38	7/28/2023	COMPETING CONTINUATION	$674,244
2023	2021	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	37	10/12/2022	NON-COMPETING CONTINUATION	-$14,456
														Subtotal = $659,788

Issue Date FY: 2021 ( Subtotal = $663,044 )
2021	2021	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	37	4/28/2021	NON-COMPETING CONTINUATION	$663,044
														Subtotal = $663,044

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2019	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	36	7/27/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $663,044 )
2019	2019	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	36	8/20/2019	NON-COMPETING CONTINUATION	$663,044
														Subtotal = $663,044

Issue Date FY: 2018 ( Subtotal = $663,044 )
2018	2018	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	35	8/10/2018	NON-COMPETING CONTINUATION	$663,044
2018	2017	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	34	12/7/2017	COMPETING CONTINUATION	$73,000
2018	2016	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	33	12/7/2017	EXTENSION WITH OR WITHOUT FUNDS	-$73,000
														Subtotal = $663,044

Issue Date FY: 2017 ( Subtotal = $652,096 )
2017	2017	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	34	7/13/2017	COMPETING CONTINUATION	$652,096
2017	2016	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	33	11/18/2016	EXTENSION WITH OR WITHOUT FUNDS	$74,026
2017	2015	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	32	11/18/2016	NON-COMPETING CONTINUATION	-$74,026
														Subtotal = $652,096

Issue Date FY: 2016 ( Subtotal = $522,333 )
2016	2016	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	33	6/10/2016	EXTENSION WITH OR WITHOUT FUNDS	$522,333
														Subtotal = $522,333

Issue Date FY: 2015 ( Subtotal = $519,120 )
2015	2015	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	32	6/19/2015	NON-COMPETING CONTINUATION	$519,120
														Subtotal = $519,120

Issue Date FY: 2014 ( Subtotal = $522,333 )
2014	2014	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	31	6/25/2014	NON-COMPETING CONTINUATION	$522,333
														Subtotal = $522,333

Issue Date FY: 2013 ( Subtotal = $504,051 )
2013	2013	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	30	6/20/2013	NON-COMPETING CONTINUATION	$504,051
														Subtotal = $504,051

Issue Date FY: 2012 ( Subtotal = $532,778 )
2012	2012	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	29	9/17/2012	COMPETING CONTINUATION	$532,778
														Subtotal = $532,778

Issue Date FY: 2010 ( Subtotal = $578,485 )
2010	2010	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	28	8/9/2010	NON-COMPETING CONTINUATION	$479,485
2010	2010	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78229	BEXAR	USA	Trans-NIH Recovery Act Research Support	000	27	12/30/2009	SUPPLEMENT FOR EXPANSION	$99,000
														Subtotal = $578,485

Issue Date FY: 2009 ( Subtotal = $484,329 )
2009	2009	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	27	6/29/2009	NON-COMPETING CONTINUATION	$484,329
														Subtotal = $484,329

Issue Date FY: 2008 ( Subtotal = $481,457 )
2008	2008	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78284	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	26	7/3/2008	NON-COMPETING CONTINUATION	$481,457
														Subtotal = $481,457

Issue Date FY: 2007 ( Subtotal = $494,213 )
2007	2007	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78284	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	25	6/21/2007	NON-COMPETING CONTINUATION	$494,213
														Subtotal = $494,213

Issue Date FY: 2006 ( Subtotal = $505,956 )
2006	2006	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78284	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	24	8/21/2006	COMPETING CONTINUATION	$505,956
														Subtotal = $505,956

Issue Date FY: 2004 ( Subtotal = $574,035 )
2004	2004	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78284	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	23	3/26/2004	NON-COMPETING CONTINUATION	$574,035
														Subtotal = $574,035

Issue Date FY: 2003 ( Subtotal = $561,280 )
2003	2003	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78284	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	22		NON-COMPETING CONTINUATION	$561,280
														Subtotal = $561,280

Issue Date FY: 2002 ( Subtotal = $549,359 )
2002	2002	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78284	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	21	4/10/2002	NON-COMPETING CONTINUATION	$549,359
														Subtotal = $549,359

Issue Date FY: 2001 ( Subtotal = $544,474 )
2001	2001	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78284	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	20	4/30/2001	COMPETING CONTINUATION	$544,474
														Subtotal = $544,474

Issue Date FY: 1999 ( Subtotal = $495,948 ) (Continued on the next page)
1999	1999	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78284	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	19	5/3/1999	SUPPLEMENT FOR EXPANSION	$72,500
Grand Total All Awards = $12,286,021

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SGLT2 Inhibitors, Ketogenesis, and Ketoacidosis

Award Number: R01DK024092

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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