Endocrinol Metab.  2017 Jun;32(2):241-247. 10.3803/EnM.2017.32.2.241.

Effects of Vildagliptin or Pioglitazone on Glycemic Variability and Oxidative Stress in Patients with Type 2 Diabetes Inadequately Controlled with Metformin Monotherapy: A 16-Week, Randomised, Open Label, Pilot Study

Affiliations
  • 1Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea. k50367@korea.ac.kr
  • 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea.

Abstract

BACKGROUND
Glycemic variability is associated with the development of diabetic complications through the activation of oxidative stress. This study aimed to evaluate the effects of a dipeptidyl peptidase 4 inhibitor, vildagliptin, or a thiazolidinedione, pioglitazone, on glycemic variability and oxidative stress in patients with type 2 diabetes.
METHODS
In this open label, randomised, active-controlled, pilot trial, individuals who were inadequately controlled with metformin monotherapy were assigned to either vildagliptin (50 mg twice daily, n=17) or pioglitazone (15 mg once daily, n=14) treatment groups for 16 weeks. Glycemic variability was assessed by calculating the mean amplitude of glycemic excursions (MAGE), which was obtained from continuous glucose monitoring. Urinary 8-iso prostaglandin F₂α, serum oxidised low density lipoprotein, and high-sensitivity C-reactive protein were used as markers of oxidative stress or inflammation.
RESULTS
Both vildagliptin and pioglitazone significantly reduced glycated hemoglobin and mean plasma glucose levels during the 16-week treatment. Vildagliptin also significantly reduced the MAGE (from 93.8±38.0 to 70.8±19.2 mg/dL, P=0.046), and mean standard deviation of 24 hours glucose (from 38±17.3 to 27.7±6.9, P=0.026); however, pioglitazone did not, although the magnitude of decline was similar in both groups. Markers of oxidative stress or inflammation including urinary 8-iso prostaglandin F₂α did not change after treatment in both groups.
CONCLUSION
In this 16-week treatment trial, vildagliptin, but not pioglitazone, reduced glycemic variability in individuals with type 2 diabetes who was inadequately controlled with metformin monotherapy, although a reduction of oxidative stress markers was not observed.

Keyword

Glycemic variability; Dipeptidyl-peptidase IV inhibitors; Thiazolidinediones; Diabetes mellitus, type 2

MeSH Terms

Blood Glucose
C-Reactive Protein
Diabetes Complications
Diabetes Mellitus, Type 2
Dipeptidyl Peptidase 4
Dipeptidyl-Peptidase IV Inhibitors
Glucose
Hemoglobin A, Glycosylated
Humans
Inflammation
Lipoproteins
Metformin*
Oxidative Stress*
Pilot Projects*
Thiazolidinediones
C-Reactive Protein
Dipeptidyl Peptidase 4
Dipeptidyl-Peptidase IV Inhibitors
Glucose
Lipoproteins
Metformin
Thiazolidinediones

Figure

  • Fig. 1 Overall study design. CGM, continuous glucose monitoring; F/U, follow-up.

  • Fig. 2 Changes of (A) mean amplitude of glycemic excursion (MAGE) and (B) standard deviation (SD) before and after 16 weeks of treatment in the vildagliptin and pioglitazone groups. aP<0.05.

  • Fig. 3 Changes of mean amplitude of glycemic excursion before and after 16 weeks of treatment in the (A) vildagliptin and (B) pioglitazone groups on individual levels.


Cited by  2 articles

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Seung-Hwan Lee, Kyung-Wan Min, Byung-Wan Lee, In-Kyung Jeong, Soon-Jib Yoo, Hyuk-Sang Kwon, Yoon-Hee Choi, Kun-Ho Yoon
Diabetes Metab J. 2021;45(3):339-348.    doi: 10.4093/dmj.2019.0203.

Comparison of Efficacy of Glimepiride, Alogliptin, and Alogliptin-Pioglitazone as the Initial Periods of Therapy in Patients with Poorly Controlled Type 2 Diabetes Mellitus: An Open-Label, Multicenter, Randomized, Controlled Study
Hae Jin Kim, In Kyung Jeong, Kyu Yeon Hur, Soo-Kyung Kim, Jung Hyun Noh, Sung Wan Chun, Eun Seok Kang, Eun-Jung Rhee, Sung Hee Choi
Diabetes Metab J. 2022;46(5):689-700.    doi: 10.4093/dmj.2021.0183.


Reference

1. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000; 321:405–412.
2. Koenig RJ, Peterson CM, Jones RL, Saudek C, Lehrman M, Cerami A. Correlation of glucose regulation and hemoglobin AIc in diabetes mellitus. N Engl J Med. 1976; 295:417–420.
3. Hirsch IB, Brownlee M. Should minimal blood glucose variability become the gold standard of glycemic control? J Diabetes Complications. 2005; 19:178–181.
4. Brownlee M, Hirsch IB. Glycemic variability: a hemoglobin A1c-independent risk factor for diabetic complications. JAMA. 2006; 295:1707–1708.
5. Monnier L, Mas E, Ginet C, Michel F, Villon L, Cristol JP, et al. Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA. 2006; 295:1681–1687.
6. Rizzo MR, Barbieri M, Marfella R, Paolisso G. Reduction of oxidative stress and inflammation by blunting daily acute glucose fluctuations in patients with type 2 diabetes: role of dipeptidyl peptidase-IV inhibition. Diabetes Care. 2012; 35:2076–2082.
7. Shimabukuro M, Higa N, Chinen I, Yamakawa K, Takasu N. Effects of a single administration of acarbose on postprandial glucose excursion and endothelial dysfunction in type 2 diabetic patients: a randomized crossover study. J Clin Endocrinol Metab. 2006; 91:837–842.
8. McCulloch DK, Kurtz AB, Tattersall RB. A new approach to the treatment of nocturnal hypoglycemia using alpha-glucosidase inhibition. Diabetes Care. 1983; 6:483–487.
9. Marfella R, Barbieri M, Grella R, Rizzo MR, Nicoletti GF, Paolisso G. Effects of vildagliptin twice daily vs. sitagliptin once daily on 24-hour acute glucose fluctuations. J Diabetes Complications. 2010; 24:79–83.
10. Mori Y, Itoh Y, Obata T, Tajima N. Effects of pioglitazone vs glibenclamide on postprandial increases in glucose and triglyceride levels and on oxidative stress in Japanese patients with type 2 diabetes. Endocrine. 2006; 29:143–148.
11. Service FJ, Molnar GD, Rosevear JW, Ackerman E, Gatewood LC, Taylor WF. Mean amplitude of glycemic excursions, a measure of diabetic instability. Diabetes. 1970; 19:644–655.
12. Service FJ. Glucose variability. Diabetes. 2013; 62:1398–1404.
13. Nalysnyk L, Hernandez-Medina M, Krishnarajah G. Glycaemic variability and complications in patients with diabetes mellitus: evidence from a systematic review of the literature. Diabetes Obes Metab. 2010; 12:288–298.
14. Kim HS, Shin JA, Lee SH, Kim ES, Cho JH, Son HY, et al. A comparative study of the effects of a dipeptidyl peptidase-IV inhibitor and sulfonylurea on glucose variability in patients with type 2 diabetes with inadequate glycemic control on metformin. Diabetes Technol Ther. 2013; 15:810–816.
15. Anderson JH Jr, Brunelle RL, Keohane P, Koivisto VA, Trautmann ME, Vignati L, et al. Mealtime treatment with insulin analog improves postprandial hyperglycemia and hypoglycemia in patients with non-insulin-dependent diabetes mellitus. Multicenter Insulin Lispro Study Group. Arch Intern Med. 1997; 157:1249–1255.
16. Wentholt IM, Kulik W, Michels RP, Hoekstra JB, DeVries JH. Glucose fluctuations and activation of oxidative stress in patients with type 1 diabetes. Diabetologia. 2008; 51:183–190.
17. Ceriello A, Esposito K, Piconi L, Ihnat MA, Thorpe JE, Testa R, et al. Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients. Diabetes. 2008; 57:1349–1354.
18. Standl E, Schnell O, Ceriello A. Postprandial hyperglycemia and glycemic variability: should we care? Diabetes Care. 2011; 34:Suppl 2. S120–S127.
19. Agarwal R. Anti-inflammatory effects of short-term pioglitazone therapy in men with advanced diabetic nephropathy. Am J Physiol Renal Physiol. 2006; 290:F600–F605.
20. Ceolotto G, Gallo A, Papparella I, Franco L, Murphy E, Iori E, et al. Rosiglitazone reduces glucose-induced oxidative stress mediated by NAD(P)H oxidase via AMPK-dependent mechanism. Arterioscler Thromb Vasc Biol. 2007; 27:2627–2633.
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