Multicenter, Open-Label, 2-Arm, Pilot Trial for Safe Reduction of Basal Insulin Dose Combined with SGLT2 Inhibitor in Type 1 Diabetes Mellitus: Study Protocol for a RISING-STAR Trial.
SGLT2 inhibitor
Type 1 diabetes mellitus
hypoglycemia
insulin dose
ketoacidosis
ketone body
ketosis
Journal
Clinical medicine insights. Endocrinology and diabetes
ISSN: 1179-5514
Titre abrégé: Clin Med Insights Endocrinol Diabetes
Pays: United States
ID NLM: 101578235
Informations de publication
Date de publication:
2021
2021
Historique:
received:
03
05
2021
accepted:
23
07
2021
entrez:
4
10
2021
pubmed:
5
10
2021
medline:
5
10
2021
Statut:
epublish
Résumé
The safe method of instructing insulin dose reduction in combination with SGLT2 inhibitors, dapagliflozin for patients with type 1 diabetes mellitus has not been clarified. In this study, we conducted a stratified, 2-arm, parallel comparative study with the primary endpoint of decreasing the frequency of hypoglycemia by instructing basal insulin dose reduction. The study has a multicenter, open-label, 2-arm design; 60 type 1 diabetes mellitus patients are being recruited from 7 hospitals. Study subjects have been stratified into 2 groups based on the ratio of basal insulin daily dose (Basal) to total daily insulin dose (TDD). The subjects whose Basal/TDD ratio is <0.4 are instructed not to reduce Basal but to reduce bolus insulin dose by 10% (group A), and subjects with a Basal/TDD ratio >0.4 will be instructed to reduce Basal by 10% (group B). The primary outcome is the daily frequency of hypoglycemia during the intervention period (SGLT2 inhibitor administration), as determined by self-monitoring of blood glucose. We aimed to confirm a greater reduction in frequency of hypoglycemia in group B (reduced Basal), than in group A (non-reduction of Basal and reduced insulin effect levels by 10%). Baseline hypoglycemia was set at 7 ± 6 times/month. The minimum sample size required to achieve a significance of .05 for a 1-sided In this pilot study, we assumed that, given a sufficient Basal, hypoglycemia would be more frequent in patients with type 1 diabetes when combined with SGLT2 inhibitors, provided the Basal was not reduced.
Sections du résumé
BACKGROUND
BACKGROUND
The safe method of instructing insulin dose reduction in combination with SGLT2 inhibitors, dapagliflozin for patients with type 1 diabetes mellitus has not been clarified. In this study, we conducted a stratified, 2-arm, parallel comparative study with the primary endpoint of decreasing the frequency of hypoglycemia by instructing basal insulin dose reduction.
METHODS
METHODS
The study has a multicenter, open-label, 2-arm design; 60 type 1 diabetes mellitus patients are being recruited from 7 hospitals. Study subjects have been stratified into 2 groups based on the ratio of basal insulin daily dose (Basal) to total daily insulin dose (TDD). The subjects whose Basal/TDD ratio is <0.4 are instructed not to reduce Basal but to reduce bolus insulin dose by 10% (group A), and subjects with a Basal/TDD ratio >0.4 will be instructed to reduce Basal by 10% (group B). The primary outcome is the daily frequency of hypoglycemia during the intervention period (SGLT2 inhibitor administration), as determined by self-monitoring of blood glucose. We aimed to confirm a greater reduction in frequency of hypoglycemia in group B (reduced Basal), than in group A (non-reduction of Basal and reduced insulin effect levels by 10%). Baseline hypoglycemia was set at 7 ± 6 times/month. The minimum sample size required to achieve a significance of .05 for a 1-sided
DISCUSSION
CONCLUSIONS
In this pilot study, we assumed that, given a sufficient Basal, hypoglycemia would be more frequent in patients with type 1 diabetes when combined with SGLT2 inhibitors, provided the Basal was not reduced.
Identifiants
pubmed: 34602832
doi: 10.1177/11795514211040539
pii: 10.1177_11795514211040539
pmc: PMC8482353
doi:
Types de publication
Journal Article
Langues
eng
Pagination
11795514211040539Informations de copyright
© The Author(s) 2021.
Déclaration de conflit d'intérêts
Declaration of conflicting interests: M. H. received grants from Asahi Kasei Pharma, Nippon Boehringer Ingelheim Co. Ltd., Mitsubishi Tanabe Pharma Corp., Daiichi Sankyo Co. Ltd., Sanofi K.K., Takeda Pharma Co. Ltd., Astellas Pharma Inc., Kyowa Kirin Co. Ltd., Sumitomo Dainippon Pharma Co. Ltd., Novo Nordisk Pharma Ltd., and Eli Lilly Japan KK, outside the submitted work. M. A. received personal fees from Novo Nordisk Pharma Ltd., Abbott Japan Co. Ltd., AstraZeneca plc, Kowa Pharma Co. Ltd., Ono Pharma Co. Ltd., Sumitomo Dainippon Pharma Co. Ltd., and Takeda Pharma Co. Ltd., outside the submitted work. M. Y. received personal fees from MSD K.K., Sumitomo Dainippon Pharma Co. Ltd., Kowa Pharma Co. Ltd., AstraZeneca plc., Takeda Pharma Co. Ltd, Kyowa Kirin Co. Ltd., Daiichi Sankyo Co. Ltd., Kowa Pharma Co. Ltd., and Ono Pharma Co. Ltd., outside the submitted work. Y. H. received grants from Asahi Kasei Pharma and personal fees from Daiichi Sankyo Co. Ltd., Mitsubishi Tanabe Pharma Corp., Sanofi K.K., and Novo Nordisk Pharma Ltd., outside the submitted work. M. F. received grants from Nippon Boehringer Ingelheim Co. Ltd., Kissei Pharma Co. Ltd., Mitsubishi Tanabe Pharma Corp., Daiichi Sankyo Co. Ltd., Sanofi K.K., Takeda Pharma Co. Ltd., Astellas Pharma Inc., MSD K.K., Kyowa Kirin Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Kowa Pharma Co. Ltd., Novo Nordisk Pharma Ltd., Ono Pharma Co. Ltd., Sanwa Kagaku Kenkyusho Co. Ltd., Eli Lilly Japan KK, Taisho Pharma Co., Ltd., Terumo Corp., Tejin Pharma Ltd., Nippon Chemiphar Co. Ltd., Abbott japan Co. Ltd., and Johnson & Johnson K.K. Medical Co. and received honoraria from Nippon Boehringer Ingelheim Co. Ltd., Kissei Pharma Co. Ltd., Mitsubishi Tanabe Pharma Corp., Daiichi Sankyo Co. Ltd., Sanofi K.K., Takeda Pharma Co. Ltd., Astellas Pharma Inc., MSD K.K., Kyowa Kirin Co. Ltd., Sumitomo Dainippon Pharma Co. Ltd., Kowa Pharma Co. Ltd., Novo Nordisk Pharma Ltd., Ono Pharma Co. Ltd., Sanwa Kagaku Kenkyusho Co. Ltd., Eli Lilly Japan K.K., Taisho Pharma Co. Ltd., Bayer Yakuhin, Ltd., AstraZeneca K.K., Mochida Pharma Co. Ltd., Abbott Japan Co. Ltd., Teijin Pharma Ltd., Arkray Inc., Medtronic Japan Co. Ltd., and Nipro Corp., outside the submitted work. The other authors declare that they have no competing interests.
Références
Diabetes Care. 2019 Jan;42(Suppl 1):S90-S102
pubmed: 30559235
N Engl J Med. 2017 Dec 14;377(24):2337-2348
pubmed: 28899222
Diabetes Care. 1997 Sep;20(9):1347-52
pubmed: 9283776
Spec Top Endocrinol Metab. 1982;4:1-27
pubmed: 6820732
Diabetes Care. 2018 Sep;41(9):1970-1980
pubmed: 29937430
Diabetes Care. 2018 Dec;41(12):2560-2569
pubmed: 30287422
BMJ. 2019 Apr 9;365:l1328
pubmed: 30967375
J Am Soc Nephrol. 2018 Nov;29(11):2755-2769
pubmed: 30314978
Nutrients. 2018 Jan 22;10(1):
pubmed: 29361766
Endocr Pract. 2010 May-Jun;16(3):428-32
pubmed: 20061290
Diabetes Care. 2018 Sep;41(9):1938-1946
pubmed: 30026335
Lancet Diabetes Endocrinol. 2019 Dec;7(12):949-958
pubmed: 31585721
MMWR Morb Mortal Wkly Rep. 2018 Mar 30;67(12):362-365
pubmed: 29596400
Diabetes Care. 2016 Apr;39(4):502-10
pubmed: 27208366
Diabetes Care. 2011 Sep;34(9):2015-22
pubmed: 21816980
Diabetes Obes Metab. 2019 Apr;21 Suppl 2:62-77
pubmed: 31081593
J Diabetes Investig. 2015 Jan;6(1):87-90
pubmed: 25621137
Lancet Diabetes Endocrinol. 2017 Nov;5(11):864-876
pubmed: 28919061
Endocr Pract. 2008 Dec;14(9):1095-101
pubmed: 19158048
Diabetes Care. 2018 Sep;41(9):1981-1990
pubmed: 29937431
Diabetes Care. 2017 Dec;40(12):1756-1762
pubmed: 29138273
Diabetes Care. 2015 Dec;38(12):2258-65
pubmed: 26486192
Diabetes Obes Metab. 2015 Oct;17(10):928-35
pubmed: 26080652
Curr Clin Pharmacol. 2018;13(4):261-272
pubmed: 30084335
Int J Pediatr Endocrinol. 2012 Jun 20;2012(1):19
pubmed: 22716962
Diabetes Care. 2011 May;34(5):1089-90
pubmed: 21430086
Diabetes Care. 2020 Jan;43(1):90-97
pubmed: 31601640