Antidiabetic drug
An antidiabetic (plural antidiabetic ) is a drug used to treat diabetes mellitus .
There are several groups of substances with different modes of action and areas of application. A basic distinction is made between insulin , insulinotropic (beta-cytotropic) and non-insulinotropic (non-beta-cytotropic) antidiabetic drugs.
The majority of the drugs in the last two groups - with a few exceptions - are assigned to the group of oral antidiabetic drugs due to their administration as tablets, capsules or dragees .
insulin
If there is an absolute or relative deficiency in the body's own insulin , which cannot be adequately treated with oral antidiabetic drugs, this must be replaced by artificial insulin preparations . Historically, these were obtained from the pancreas of slaughtered animals. Today, insulin is almost exclusively produced recombinantly (i.e. genetically ) and is largely produced analogously to humans, i.e. H. with the human and not an animal amino acid sequence and with a human-analogous glycosylation pattern .
Insulinotropic antidiabetic drugs
Insulinotropic antidiabetics increase the release of insulin from the beta cells of the pancreas and thus treat a secretion deficit. The effect can decrease in later stages of the disease, as the function of the beta cell can be exhausted with increasing duration of the disease.
Sulfonylureas
Sulphonylureas stimulate insulin secretion in the beta cells of the pancreas, which lowers blood sugar levels. If there is a significant insulin deficiency due to exhaustion of the pancreas (so-called secondary failure), insulin therapy usually has to be started. Well-known representatives are glibenclamid and glimepiride .
Gliptins (DPP4 inhibitors)
The gliptins act as inhibitors of the enzyme dipeptidyl peptidase 4 (DPP4) via the incretin effect . The inhibition of DPP4 stops the breakdown of the body's own peptide glucagon-like peptide 1 (GLP1), which, like blood sugar-increasing glucagon, is formed by peptide cleavage from preproglucagon, the glucagon precursor protein made up of 180 amino acids. After its release from the peptide, however, GLP1 acts as a glucagon antagonist by suppressing the further secretion of preproglucagon in a feedback mechanism. In addition, GLP1 also stimulates the release of insulin . Approved active substances are sitagliptin , vildagliptin and saxagliptin .
Incretin mimetics (GLP1 receptor agonists)
The incretin mimetics also work via the incretin effect , but in contrast to the gliptins by simulating the effect of GLP1 on its receptor and not by inhibiting its breakdown. Incretin mimetics also have a weight-reducing effect. The approved incretin mimetics exenatide , liraglutide , dulaglutide , albiglutide and semaglutide are polypeptides and are not oral antidiabetic drugs, but are injected subcutaneously.
Glinide (sulfonylurea analogs)
Glinides are sulfonylurea analogs and their importance has now receded into the background. The group of glinides consists of two substances, the effect of which is a quick and short-term release of insulin. Repaglinide has been approved on the German market since 1999 and nateglinide since 2000. Since February 18, 2016, however, glinides in Germany can only be reimbursed by the statutory health insurance in medically justified individual cases , as their benefit has not been sufficiently proven in studies.
Non-insulinotropic antidiabetic drugs
Non-insulinotropic antidiabetic drugs act in the periphery and treat insulin resistance (biguanides, glitazones), delay the absorption of glucose from the intestine (α-glucosidase inhibitors) or promote the excretion of glucose via the kidneys (SGLT-2 inhibitors). There is no risk of hypoglycemia and the drugs are particularly suitable for obese patients as they do not lead to weight gain.
Biguanide (metformin)
Biguanides inhibit the formation of new glucose ( gluconeogenesis ) in the liver cells . They reduce the absorption of glucose from the intestine and increase its utilization in the body periphery, e.g. B. in the muscles. Metformin is the only currently approved active ingredient from the group of biguanides. Metformin is indicated when type 2 diabetes, changes in diet and exercise do not lead to the individual HbA1c goal. Contraindications include ketoacidosis and other chronic metabolic disorders as well as diabetes-related complications and serious comorbidities.
α-glucosidase inhibitors
By inhibiting α-glucosidase, α-glucosidase inhibitors delay the absorption of carbohydrates and thus glucose uptake from the intestine into the blood, thereby reducing blood sugar peaks after meals rich in carbohydrates. The substances approved for type 2 diabetes are acarbose , miglitol and voglibose . It is advantageous that α-glucosidase inhibitors (in contrast to insulin or sulfonylureas) do not cause hypoglycaemia.
Gliflozine (SGLT-2 inhibitor)
The gliflozins are inhibitors of the SGLT2 carrier and thus promote the excretion of glucose via the kidneys, as they prevent the proximal reabsorption of glucose via this carrier. This leads directly to an increased excretion of glucose in the urine and to a lowering of the blood sugar level. Approved substances are canagliflozin , dapagliflozin , empagliflozin and ertugliflozin .
Amylin analogs
Amylin , also known as islet amyloid polypeptide (IAPP), is a peptide hormone that is normally produced by the β cells of the pancreas together with insulin (but only in one hundredth of the amount) at meals. Like GLP1, it inhibits glucagon secretion after eating. In diabetics, the release of amylin is reduced, which can be compensated by amylin analogues. Pramlintide (US trade name: Symlin ) is an analogue of the hormone amylin and has been approved in the USA for the treatment of both type 1 and type 2 diabetics. Pramlintide is the first drug approved for type 1 diabetics since insulin.
Glitazone (insulin sensitizer)
Like glinides, glitazones have largely receded into the background as a substance class today. They improve the effect of the body's own insulin with the help of an increase in the synthesis of the glucose-absorbing GLUT4 receptors, the main peripheral target of insulin, and thereby reduce insulin resistance in type 2 diabetes. Although the group comprises more than 10 substances, only the active ingredient pioglitazone has been approved in Germany since June 2011 . Since April 2011 it can only be prescribed in justified exceptional cases at the expense of the statutory health insurance and the Federal Institute for Drugs and Medical Devices advises against taking it due to an increased risk of cancer.
Web links
Individual evidence
- ↑ Herold: Internal Medicine. 2011.
- ↑ G-BA press release of February 18, 2016, accessed on April 13, 2016 .
- ↑ Richard Daikeler, idols Use, Sylke Waibel: diabetes. Evidence-based diagnosis and therapy. 10th edition. Kitteltaschenbuch, Sinsheim 2015, ISBN 978-3-00-050903-2 , p. 33.
- ↑ Richard Daikeler, idols Use, Sylke Waibel: diabetes. Evidence-based diagnosis and therapy. 10th edition. Kitteltaschenbuch, Sinsheim 2015, ISBN 978-3-00-050903-2 , pp. 41–43.
- ↑ G. Ryan, TA Briscoe, L. Jobe: Review of pramlintide as adjunctive therapy in treatment of type 1 and type 2 diabetes. In: Drug Des Devel Ther. 2, Feb 6, 2009, pp. 203-214. PMID 19920907
- ↑ Diabetes: Pioglitazone goes off the market due to cancer risk ( Memento of the original from June 18, 2011 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. , Deutsches Ärzteblatt, June 10, 2011.
