Metformin – bei Typ-2-Diabetes das Mittel der ersten Wahl?!

Zusammenfassung

Diabetes mellitus und Prädiabetes haben in Deutschland eine sehr hohe Prävalenz. Obwohl körperliche Aktivität und nutritive Intervention sich als wirksam erwiesen haben, bleibt das blutzuckersenkende Metformin das Mittel der ersten Wahl. Das Medikament interferiert mit Mikronährstoffen wie B-Vitaminen, Vitamin D und Magnesium und kann den bei Typ-2-Diabetiker*innen oft bestehenden Nährstoffmangel noch verstärken. Daraus resultieren u. a. negative Folgen für Energiestoffwechsel, Immunsystem, Inflammation und Insulinresistenz sowie ein Anstieg des gefäßschädigenden Homocysteins. Halbjährliche Kontrollen der Homocystein-, Methylmalonsäure- und Vitamin-D-Spiegel sind bei Typ-2-Diabetes ratsam. Inbs. bei Metformintherapie bzw. Polymedikation sollten die Mikronährstoffmängel durch tägliche Supplementierung ausgeglichen werden.

Schlüsselwörter

Typ-2-Diabetes - Metformin - Prädiabetes - Mikronährstoffmangel - B-Vitamine - Homocystein - Vitamin D - Magnesium - Supplementierung - Schlaganfallrisiko

• Literatur

• 1 Saeedi P, Petersohn I, Salpea P. et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th ed. Diabetes Res Clin Pract 2019; 157: 107843
• 2 Armstrong DG, Boulton AJM, Bus SA. Diabetic foot ulcers and their recurrence. N Engl J Med 2017; 376 (24) : 2367-2375
• 3 Statistisches Bundesamt. Statistisches Jahrbuch. Deutschland und Internationales 2019; Kapitel 4 Gesundheit.. https://www.destatis.de/DE/Themen/Querschnitt/Jahrbuch/statistisches-jahrbuch-2019-dl.pdf?__blob=publicationFile (Stand: 09.08.2021)
• 4 Oetzel S.W. „Zucker“ droht – Wie die Manifestation eines Diabetes mellitus Typ 2 verhindert werden kann. DAZ online 2019; 26. https://www.deutsche-apotheker-zeitung.de/daz-az/2019/daz-26-2019/wenn-zucker-droht (Stand: 09.08.2021)
• 5 Zhao B, Zang L, Zhao J. et al. Association of Magnesium Intake With Type 2 Diabetes and Total Stroke: An Updated Systematic Review and Meta-Analysis. BMJ Open 2020; 10 (03) : e032240
• 6 Bhatt DL, Steg PG, Miller M. et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med 2019; 380 (01) : 11-22
• 7 Gröber U, Holick MF. Diabetes Prevention: Vitamin D Supplementation May Not Provide Any Protection If There Is No Evidence of Deficiency! Nutrients. 2019; 11: 2651 ; doi:10.3390/nu11112651
• 8 Pittas AG, Dawson-Hughes B, Sheehan P. et al. Vitamin D Supplementation and Prevention of Type 2 Diabetes. N Engl J Med 2019; 381 (06) : 520-530
• 9 Knowler WC, Barrett-Connor E, Fowler SE. et al. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346: 393-403
• 10 Diabetes Prevention Program Research Group.. Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over 15-year follow-up: the Diabetes Prevention Program Outcomes Study. Lancet Diabetes Endocrinol 2015 3. 866-875
• 11 Salpeter SR, Buckley NS, Kahn JA, Salpeter EE. Meta-analysis: metformin treatment in persons at risk for diabetes mellitus. Am J Med 2008; 121: 149-157.e2
• 12 Svensson E, Baggesen LM, Johnsen SP. et al. Early Glycemic Control and Magnitude of HbA1c Reduction Predict Cardiovascular Events and Mortality: Population-Based Cohort Study of 24,752 Metformin Initiators. Diabetes Care 2017; 40: 800-807
• 13 UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998; 352 (9131): 854-865
• 14 Gnesin F, Thuesen AC, Kähler LK. et al. Metformin monotherapy for adults with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2020 6. CD012906.
• 15 Bundesärztekammer (BÄK), Kassenärztliche Bundesvereinigung (KBV), Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF). Nationale Versorgungsleitlinie Typ-2-Diabetes – Teilpublikation der Langfassung, 2. Auf.,. 2021 https://www.leitlinien.de/themen/diabetes/pdf/diabetes-2aufl-vers1.pdf (Stand: 09.08.2021)
• 16 Mutschler E. Arzneimittelwirkungen. Pharmakologie – Klinische Pharmakologie – Toxikologie. . 11., neu bearb. Aufl.. Stuttgart:: Wissenschaftliche Verlagsgesellschaft; 2020
• 17 Gröber U. COVID-19 und Long-COVID. Bessere Resilienz mit immunrelevanten Mikronährstoffen. . Stuttgart: Wissenschaftliche Verlagsgesellschaft; 2021
• 18 Thornalley PJ, Babaei-Jadidi R, Al Ali H. et al. High prevalence of low plasma thiamine concentration in diabetes linked to a marker of vascular disease. Diabetologia. 2007; 50 (10) : 2164-2170
• 19 Valette G, Ribes G, Rondot AM. et al. Effect of cocarboxylase on hyperlactatemia and hyperpyruvicemia induced by phenformin in dogs. C R Seances Soc Biol Fil 1975; 169 (01) : 121-125
• 20 Calabrese AT, Coley KC, DaPos SV. et al. Evaluation of prescribing practices: risk of lactic acidosis with metformin therapy. Arch Intern Med 2002; 162 (04) : 434-437
• 21 Alston TA. Does metformin interfere with thiamine). Arch Int Med 2003; 163 (08) : 983
• 22 Liang X, Chien H-C, Yee SW. et al. Metformin is a substrate and inhibitor of the human thiamine transporter, THTR-2 (SLC19A3). Mol Pharm 2015; 12 (12) : 4301-4310
• 23 Vora B, Green EA, Khuri N. et al. Drug-nutrient interactions: discovering prescription drug inhibitors of the thiamine transporter ThTR-2 (SLC19A3). Am J Clin Nutr 2020; 111 (01) : 110-121
• 24 Kodentsova VM, Alekseeva IA, Spirichev VB. Riboflavin metabolism in diabetes mellitus. Ukr Biokhim Zh 1978; 64 (04) : 105-108
• 25 Porter KM, Ward M, Hughes CF. et al. Hyperglycemia and Metformin Use Are Associated With B Vitamin Deficiency and Cognitive Dysfunction in Older Adults. J Clin Endocrinol Metab 2019; 104 (10) : 4837-4847
• 26 Thaku K, Tomar SK, Singh AK. et al. Riboflavin and health: A review of recent human research. Crit Rev Food Sci Nutr 2017; 57 (17) : 3650-3660
• 27 Alam MM, Iqbal S, Naseem I. et al. Ameliorative effect of riboflavin on hyperglycemia, oxidative stress and DNA damage in type-2 diabetic mice: Mechanistic and therapeutic strategies. Arch Biochem Biophys 2015; 584: 10-19
• 28 Suwannasom N, Kao I, Pruß A. et al. Riboflavin: The Health Benefits of a Forgotten Natural Vitamin. Int J Mol Sci 2020; 21 (03) : 950
• 29 Malaguarnera G, Gagliano C, Salomone S. et al. Folate status in type 2 diabetic patients with and without retinopathy. Clin Ophthalmol 2015; 9: 1437-1442
• 30 Wulffele MG, Kooy A, Lehert P. et al. Effects of short-term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B₁₂ in T2DM mellitus: a randomized, placebo-controlled trial. J Intern Med 2003; 254 (05) : 455-463
• 31 Sahin M, Tutuncu NB, Ertugrul D. et al. Effects of metformin or rosiglitazone on serum concentrations of homocysteine, folate, and vitamin B₁₂ in patients with T2DM mellitus. J Diabetes Complicat 2017; 21 (02) : 118-123
• 32 Van Etten R, de Koning E, Verhaar M. et al. Impaired NO-dependent vasodilation in patients with Type II (non-insulin-dependent) diabetes mellitus is restored by acute administration of folate. Diabetologia. 2002; 45 (07) : 1004-1010
• 33 MacKenzie KE, Wiltshire EJ, Gent R. et al. Folate and vitamin B₆ rapidly normalize endothelial dysfunction in children with type 1 diabetes mellitus. Pediatrics. 2006; 118 (01) : 242-253
• 34 Peng HY, Man CF, Xu J. et al. Elevated homocysteine levels and risk of cardiovascular and all-cause mortality: a meta-analysis of prospective studies. J Zhejiiang Univ Sci B 2015; 16 (01) : 78-86
• 35 Lind MV, Lauritzen L, Kristensen M. et al. Effect of folate supplementation on insulin sensitivity and type 2 diabetes: a meta-analysis of randomized controlled trials. Am J Clin Nutr 2019; 109 (01) : 29-42
• 36 Gröber U, Kisters K, Schmidt J. Neuroenhancement with Vitamin B₁₂: Underestimated neurological significance. Nutrients. 2013; 5 (12) : 5031-5045
• 37 Gröber U, Kisters K, Schmidt J. Important drug-micronutrient interactions: A selection for clinical practice. Crit Rev Food Sci Nutr 2018; 60 (02) : 257-275
• 38 Al-Hamdi A, Al-Gahhafi M, Al-Roshdi S. et al. Vitamin B₁₂ Deficiency in Diabetic Patients on Metformin Therapy: A cross-sectional study from Oman. Sultan Qaboos Univ Med J. 2020; 20 (01) : e90-e94
• 39 Shivaprasad C, Gautham K, Ramdas B. et al. Metformin Usage Index and assessment of vitamin B₁₂ deficiency among metformin and non-metformin users with type 2 diabetes mellitus. Acta Diabetol 2020; 57 (09) : 1073-1080
• 40 Sakyi SA, Laing EF, Mantey R. Profiling immuno-metabolic mediators of vitamin B₁₂ deficiency among metformin-treated type 2 diabetic patients in Ghana. PLoS One 2021; 16 (03) : e0249325
• 41 Infante M, Leoni M, Caprio M, Fabbri A. Long-term metformin therapy and vitamin B₁₂ deficiency: An association to bear in mind. World J Diabetes 2021; 12 (07) : 916-931
• 42 Gröber U, Holick MF. Vitamin D – Die Heilkraft des Sonnenvitamins. 4.. , aktual. u. erw. Aufl. Stuttgart: Wissenschaftliche Verlagsgesellschaft; 2020
• 43 Gröber U, Holick MF. Diabetes Prevention: Vitamin D Supplementation May Not Provide Any Protection If There Is No Evidence of Deficiency! Nutrients. 2019 11. 2651 .
• 44 Sohl E, van Schoor NM, de Jongh RT. et al. The impact of medication on vitamin D status in older individuals. Eur J Endocrinol 2012; 166 (03) : 477-485
• 45 Gröber U. Magnesium and Drugs. Int J Mol Sci 2019; 20 (09) : 2094
• 46 Gröber U, Schmidt J, Kisters K. Magnesium in Prevention and Therapy. Nutrients 2015; 7 (09) : 8199-8226
• 47 Palmer BF, Clegg DJ. Electrolyte and acid-base disturbances in patients with diabetes mellitus. N Engl J Med 2015; 373 (06) : 548-559
• 48 Gröber U. Common drugs as micronutrient disruptors: A selection for clinical practice. Ann Epidemiol Public Health 2020; 3 (01) : 1014-1031
• 49 Zhao B, Zang L, Zhao J. et al. Association of Magnesium Intake With Type 2 Diabetes and Total Stroke: An Updated Systematic Review and Meta-Analysis. BMJ Open 2020; 10 (03) : e032240