Synergism in Combined Use of Oral Antihyperglycemic Drugs
The aim of the investigation was to study the capabilities of combined use of metformin and vildagliptin, and its effect on glycemia and oxidative stress parameters in patients with newly diagnosed type 2 diabetes mellitus (DM 2).
Materials and Methods. The study involved 37 patients with DM 2, they were divided (after two-week metformin dose titration) into two groups by simple random sampling. Group 1 patients (n=18) were administered metformin at a dose of 1700 mg a day, group 2 patients (n=19) — the combination of metformin (1000 mg a day) with vildagliptin (50 mg a day). Group 3 — a control group (n=20) consisted of subjects without carbohydrate metabolism imbalance. We studied glycemia indices (fasting blood plasma glucose, glycosylated hemoglobin), the level of molecular products of lipid peroxidation (diene and triene conjugates, malon dialdehyde), intensity of oxidative protein modification by the level of carbonyl derivatives, syperoxide dismutase and catalase activity before and 3 months after therapy.
Results. Combined use of metformin (1000 mg a day) and vildagliptin (50 mg a day) in patients with newly diagnosed DM 2 showed the synergism of their antihyperglycemic and antioxidant effect. The mentioned combination of drugs compared to metformin monotherapy (1700 mg a day) enables to reduce side effect rate and significantly increase catalase activity.
Conclusion. The results of combined use of metformin and vildagliptin demonstrated the capability of DM 2 therapy based on rational choice of the combination of antihyperglycemic drugs relying on their synergistic properties.
- Nikonova T.V. Slow-release Metformin (Glucophage Long) in management of type 2 diabetes mellitus. Farmateka 2012; 3: 49.
- Esteghamati A., Eskandari D., Mirmiranpour H., et al. Effects of metformin on markers of oxidative stress and antioxidant reserve in patients with newly diagnosed type 2 diabetes: a randomized clinical trial. Clin Nutr 2013; Apr; 32(2): 179–185, http://dx.doi.org/10.1016/j.clnu.2012.08.006.
- Rizzo M.R., 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 Oct; 35(10): 2076–2082, http://dx.doi.org/10.2337/dc12-0199.
- Pala L., Ciani S., Dicembrini I., et al. Relationship between GLP-1 levels and dipeptidyl peptidase-4 activity in different glucose tolerance conditions. Diabetic Med 2010; 27(6): 691–695, http://dx.doi.org/10.1111/j.1464-5491.2010.03010.x.
- Hamamoto S., Kanda Y., Shimoda M., et al. Vildagliptin preserves the mass and function of pancreatic β cells via the developmental regulation and suppression of oxidative and endoplasmic reticulum stress in a mouse model of diabetes. Diabetes Obes Metab 2013; 15: 153–163, http://dx.doi.org/10.1111/dom.12005.
- Hinke S.A., Kuhn-Wache K., Hoffmann T., et al. Metformin effects on dipeptidilpeptidase IV degradation of glucagon-like peptide-1. Biochemical Biophys Res Commun 2002; 291: 1302–1308, http://dx.doi.org/10.1006/bbrc.2002.6607.
- Yasuda N., Inoue T., Nagakura T., et al. Enchanced secretion of glucagon-like peptide-1 by biguanide compounds. Biochemical Biophys Res Commun 2002; 298: 779–784, http://dx.doi.org/10.1016/S0006-291X(02)02565-2.
- Mannucci E., Ognibene A., Cremasco F., et al. Effect of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels in obese nondiabetic subjects. Diabetes Care 2001; 24: 489–494.
- Maida A., Lamont B.J., Cao X. Metformin regulates the incretin receptor axis via a pathway dependent on peroxisome proliferator-activated receptor-a in mice. Diabetologia 2011 Feb; 54(2): 339–349, http://dx.doi.org/10.1007/s00125-010-1937-z.
- Halimi S., Schweizer A., Minic B., et al. Combination treatment in the management of type 2 diabetes: focus on vildagliptin and metformin as a single tablet. Vasc Health Risk Manag 2008; 4(3): 481–492.
- Algoritmy spetsializirovannoy meditsinskoy pomoshchi bol'nym sakharnym diabetom [Algorithms of specialized medical aid for diabetic subjects]. Pod red. Dedova I.I., Shestakovoy M.V. [Dedov I.I., Shestakova M.V. (editors)]. Moscow; 2013; 120 p.
- Pavlović D., Kocić R., Kocić G., et al. Effect of four-week metformin treatment on plasma and erythrocyte antioxidative defense enzymes in newly diagnosed obese patients with type 2 diabetes. Diabetes Obes Metab 2000 Aug; 2(4): 251–256, http://dx.doi.org/10.1046/j.1463-1326.2000.00089.x.
- Men’shchikova E.B., Zenkov N.K., Lankin V.Z., et al. Okislitel’nyy stress: patologicheskie sostoyaniya i zabolevaniya [Oxidative stress: pathological conditions and diseases]. Novosibirsk; 2008; 284 p.
