Download PDF
Exp Clin Endocrinol Diabetes 2020; 128(08): 506-511
DOI: 10.1055/a-0664-7583
Article

Effect of Dapagliflozin on Insulin Secretion and Insulin Sensitivity in Patients with Prediabetes

Alejandra M. Ramírez-Rodríguez
1   Institute of Experimental and Clinical Therapeutics, Department of Physiology, Health Sciences University Center, University of Guadalajara, Guadalajara, Jalisco, Mexico
,
Manuel González-Ortiz
1   Institute of Experimental and Clinical Therapeutics, Department of Physiology, Health Sciences University Center, University of Guadalajara, Guadalajara, Jalisco, Mexico
,
Esperanza Martínez-Abundis
1   Institute of Experimental and Clinical Therapeutics, Department of Physiology, Health Sciences University Center, University of Guadalajara, Guadalajara, Jalisco, Mexico
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Abstract

Aim To evaluate the effect of dapagliflozin on insulin secretion and insulin sensitivity in patients with prediabetes.

Methods A randomized, double-blind, placebo-controlled clinical trial was carried out in 24 adults diagnosed with prediabetes and without pharmacological treatment. Patients were randomly assigned into two groups of 12 patients each to receive 10 mg of oral dapagliflozin or placebo once a day during 12 weeks. At baseline and at the end of the study, anthropometric and metabolic measurements were evaluated, including the first phase of insulin secretion, total insulin secretion, and insulin sensitivity.

Results After dapagliflozin administration, there were significant decreases in body weight (80.8±16.3 vs. 77.8±14.9 kg, p=0.019), body mass index (30.3±3.5 vs. 29.2±3.1 kg/m2, p=0.023), waist circumference (100.6±13.5 vs. 96.2±11.8 cm, p=0.003), fasting glucose (5.9±0.4 vs. 5.1±0.3 mmol/L, p<0.001) and uric acid (334.3±70.8 vs. 262.9±60.7 mmol/L, p=0.032), with a tendency to increase the insulin sensitivity (1.94±0.72 vs. 2.63±1.04, p=0.064).

Conclusion Dapagliflozin administration in patients with prediabetes decreased body weight, body mass index, waist circumference, fasting glucose, and uric acid, with a tendency to increase the insulin sensitivity without changes in insulin secretion.

Key words

dapagliflozin - prediabetes - insulin secretion - insulin sensitivity - obesity


Publication History

Received: 05 May 2018
Received: 11 July 2018

Accepted: 26 July 2018

Article published online:
27 August 2018

© Georg Thieme Verlag KG
Stuttgart · New York

 

  • References

  • 1 Fioretto P, Giaccari A, Sesti G. Efficacy and safety of dapagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in diabetes mellitus. Cardiovasc Diabetol 2015; 14: 142
    CrossrefPubMedGoogle Scholar
  • 2 Kaneto H, Obata A, Kimura T. et al. Beneficial effects of sodium-glucose cotransporter 2 inhibitors for preservation of pancreatic β-cell function and reduction of insulin resistance. J Diabetes 2017; 9: 219-225
    CrossrefPubMedGoogle Scholar
  • 3 Wildinga J, Bailey C, Rigneyc U. et al. Dapagliflozin therapy for type 2 diabetes in primary care: Changes in A1C, weight and blood pressure over 2 years follow-up. Prim Care. Diabetes 2017; 11: 437-444
    PubMedGoogle Scholar
  • 4 González-Ortiz M, Méndez-Del Villar M, Martínez-Abundis E et al. Effect of dapagliflozin administration on metabolic syndrome, insulin sensitivity, and insulin secretion. Minerva Endocrinol 2016; 20:
    PubMed
  • 5 Ferrannini E. Definition of intervention points in prediabetes. Lancet Diabetes Endocrinol 2014; 2: 667-675
    CrossrefPubMedGoogle Scholar
  • 6 Edwards CM, Cusi K. Prediabetes: A Worldwide Epidemic. Endocrinol Metab Clin North Am 2016; 45: 751-764
    CrossrefPubMedGoogle Scholar
  • 7 DeFronzo RA, Abdul-Ghani M. Type 2 Diabetes Can Be Prevented With Early Pharmacological Intervention. Diabetes Care 2011; 34 (Suppl. 02) S202-S209
    CrossrefPubMedGoogle Scholar
  • 8 Madaan T, Akhtar M, Najmi AK. Sodium glucose CoTransporter 2 (SGLT2) inhibitors: Current status and future perspective. Eur J Pharm Sci 2016; 93: 244-252
    CrossrefPubMedGoogle Scholar
  • 9 American Diabetes Association . Classification and diagnosis of diabetes: Standards of medical care in diabetes-2018. Diabetes Care 2018; 41 (Suppl. 01) S13-S27
    CrossrefPubMedGoogle Scholar
  • 10 Haffner SM, Miettinen H, Gaskill SP. et al. Decreased insulin secretion and increased insulin resistance are independently related to the 7-year risk of NIDDM in Mexican-Americans. Diabetes 1995; 44: 1386-1391
    CrossrefPubMedGoogle Scholar
  • 11 Stumvoll M, Mitrakou A, Pimienta W. et al. Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity. Diabetes Care 2000; 23: 295-301
    CrossrefPubMedGoogle Scholar
  • 12 Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: Comparison with the euglycemic insulin clamp. Diabetes Care 1999; 22: 1462-1470
    CrossrefPubMedGoogle Scholar
  • 13 Matsuda M, DeFronzo RA.Matsuda index. Web calculator. [internet] http://mmatsuda.diabetes-smc.jp/MIndex.html [accessed May/25/2018]
    PubMed
  • 14 DeFronzo RA, Hompesch M, Kasichayanula S. et al. Characterization of renal glucose reabsorption in response to dapagliflozin in healthy subjects and subjects with type 2 diabetes. Diabetes Care 2013; 36: 3169-3176
    CrossrefPubMedGoogle Scholar
  • 15 Pereira MJ, Lundkvist P, Kamble PG. et al. A randomized controlled trial of dapagliflozin plus once-weekly exenatide versus placebo in individuals with obesity and without diabetes: Metabolic effects and markers associated with body weight loss. Diabetes Ther 2018; Jun 13 DOI: 10.1007/s13300-018-0449-6.
    CrossrefPubMedGoogle Scholar
  • 16 Jeyaseelan L, Rao PSS. Methods of determining sample sizes in clinical trials. Indian Pediatr 1989; 26: 115-121
    PubMedGoogle Scholar
  • 17 Mudaliar S, Henry RR, Boden G. et al. Changes in insulin sensitivity and insulin secretion with the sodium glucose cotransporter 2 inhibitor dapagliflozin. Diabetes Technol Ther 2014; 16: 137-144
    CrossrefPubMedGoogle Scholar
  • 18 Kanat M, DeFronzo RA, Abdul-Ghani MA. Treatment of prediabetes. World J Diabetes 2015; 6: 1207-1222
    CrossrefPubMedGoogle Scholar
  • 19 American Diabetes Association . Prevention or delay of type 2 diabetes: Standards of medical care in diabetes-2018. Diabetes Care 2018; 41 (Suppl. 01) S51-S54
    CrossrefPubMedGoogle Scholar
  • 20 Lundkvist P, Sjöström CD, Amini S. et al. Dapagliflozin once-daily and exenatide once-weekly dual therapy: A 24-week randomized, placebo-controlled, phase II study examining effects on body weight and prediabetes in obese adults without diabetes. Diabetes Obes Metab 2017; 19: 49-60
    CrossrefPubMedGoogle Scholar
  • 21 Bolinder J, Ljunggren Ö, Kullberg J. et al. Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin. J Clin Endocrinol Metab 2012; 97: 1020-1031
    CrossrefPubMedGoogle Scholar
  • 22 Joannides CN, Mangiafico SP, Waters MF. et al. Dapagliflozin improves insulin resistance and glucose intolerance in a novel transgenic rat model of chronic glucose overproduction and glucose toxicity. Diabetes Obes Metab 2017; 19: 1135-1146
    CrossrefPubMedGoogle Scholar
  • 23 Merovci A, Mari A, Solis C. et al. Dapagliflozin lowers plasma glucose concentration and improves β-cell function. J Clin Endocrinol Metab 2015; 100: 1927-1932
    CrossrefPubMedGoogle Scholar
  • 24 Abdul-Ghani MA, Tripathy D, DeFronzo RA. Contributions of beta-cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fasting glucose. Diabetes Care 2006; 29: 1130-1139
    CrossrefPubMedGoogle Scholar
  • 25 Santaguida PL, Balion C, Hunt D. et al. Diagnosis, prognosis, and treatment of impaired glucose tolerance and impaired fasting glucose. Evid Rep Technol Assess 2005; 128: 1-11
    PubMedGoogle Scholar