Non-insulin drugs to treat hyperglycaemia in type 1 diabetes mellitus. 2016

Christian Seerup Frandsen, and Thomas Fremming Dejgaard, and Sten Madsbad
Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark. Electronic address: Frandsenmail@gmail.com.

Insulin treatment of individuals with type 1 diabetes has shortcomings and many patients do not achieve glycaemic and metabolic targets. Consequently, the focus is on novel non-insulin therapeutic approaches that reduce hyperglycaemia and improve metabolic variables without increasing the risk of hypoglycaemia or other adverse events. Several therapies given in conjunction with insulin have been investigated in clinical trials, including pramlintide, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, sodium-glucose co-transporter inhibitors, metformin, sulfonylureas, and thiazolidinediones. These drugs have pleiotropic effects on glucose metabolism and different actions complementary to those of insulin-this Review reports the effects of these drugs on glycaemic control, glucose variability, hypoglycaemia, insulin requirements, and bodyweight. Existing studies are of short duration with few participants; evidence for the efficacy of concomitant treatments is scarce and largely clinically insignificant. A subgroup of patients with type 1 diabetes for whom non-insulin antidiabetic drugs could significantly benefit glycaemic control cannot yet be defined, but we suggest that obese patients prone to hypoglycaemia and patients with residual β-cell function are populations of interest for future trials.

UI MeSH Term Description Entries
D007004 Hypoglycemic Agents Substances which lower blood glucose levels. Antidiabetic,Antidiabetic Agent,Antidiabetic Drug,Antidiabetics,Antihyperglycemic,Antihyperglycemic Agent,Hypoglycemic,Hypoglycemic Agent,Hypoglycemic Drug,Antidiabetic Agents,Antidiabetic Drugs,Antihyperglycemic Agents,Antihyperglycemics,Hypoglycemic Drugs,Hypoglycemic Effect,Hypoglycemic Effects,Hypoglycemics,Agent, Antidiabetic,Agent, Antihyperglycemic,Agent, Hypoglycemic,Agents, Antidiabetic,Agents, Antihyperglycemic,Agents, Hypoglycemic,Drug, Antidiabetic,Drug, Hypoglycemic,Drugs, Antidiabetic,Drugs, Hypoglycemic,Effect, Hypoglycemic,Effects, Hypoglycemic
D008687 Metformin A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289) Dimethylguanylguanidine,Dimethylbiguanidine,Glucophage,Metformin HCl,Metformin Hydrochloride,HCl, Metformin,Hydrochloride, Metformin
D003922 Diabetes Mellitus, Type 1 A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence. Diabetes Mellitus, Brittle,Diabetes Mellitus, Insulin-Dependent,Diabetes Mellitus, Juvenile-Onset,Diabetes Mellitus, Ketosis-Prone,Diabetes Mellitus, Sudden-Onset,Diabetes, Autoimmune,IDDM,Autoimmune Diabetes,Diabetes Mellitus, Insulin-Dependent, 1,Diabetes Mellitus, Type I,Insulin-Dependent Diabetes Mellitus 1,Juvenile-Onset Diabetes,Type 1 Diabetes,Type 1 Diabetes Mellitus,Brittle Diabetes Mellitus,Diabetes Mellitus, Insulin Dependent,Diabetes Mellitus, Juvenile Onset,Diabetes Mellitus, Ketosis Prone,Diabetes Mellitus, Sudden Onset,Diabetes, Juvenile-Onset,Diabetes, Type 1,Insulin Dependent Diabetes Mellitus 1,Insulin-Dependent Diabetes Mellitus,Juvenile Onset Diabetes,Juvenile-Onset Diabetes Mellitus,Ketosis-Prone Diabetes Mellitus,Sudden-Onset Diabetes Mellitus
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006943 Hyperglycemia Abnormally high BLOOD GLUCOSE level. Postprandial Hyperglycemia,Hyperglycemia, Postprandial,Hyperglycemias,Hyperglycemias, Postprandial,Postprandial Hyperglycemias
D000067757 Glucagon-Like Peptide-1 Receptor A receptor for GLUCAGON-LIKE PEPTIDE 1 (GLP-1) expressed primarily on the surface of beta and ductal exocrine cells of the pancreas, as well as cells of other tissues. GLP-1 acts through GLP-1R to potentiate signaling in pancreatic cells in response to glucose-stimulated insulin secretion (GSIS). GLP-1 Receptor,GLP-1R Receptor,GLP1R Protein,GLP1R Receptor,GLP 1 Receptor,GLP 1R Receptor,Glucagon Like Peptide 1 Receptor,Peptide-1 Receptor, Glucagon-Like,Protein, GLP1R,Receptor, GLP-1,Receptor, GLP-1R,Receptor, GLP1R,Receptor, Glucagon-Like Peptide-1
D000077203 Sodium-Glucose Transporter 2 Inhibitors Compounds that inhibit SODIUM-GLUCOSE TRANSPORTER 2. They lower blood sugar by preventing the reabsorption of glucose by the kidney and are used in the treatment of TYPE 2 DIABETES MELLITUS. Gliflozin,SGLT-2 Inhibitor,SGLT2 Inhibitor,Sodium-Glucose Transporter 2 Inhibitor,Gliflozins,SGLT-2 Inhibitors,SGLT2 Inhibitors,Inhibitor, SGLT-2,Inhibitor, SGLT2,SGLT 2 Inhibitor,SGLT 2 Inhibitors,Sodium Glucose Transporter 2 Inhibitor,Sodium Glucose Transporter 2 Inhibitors
D013453 Sulfonylurea Compounds A class of compounds in which a sulfone functional group is attached to UREA. Compounds, Sulfonylurea
D045162 Thiazolidinediones THIAZOLES with two keto oxygens. Members are insulin-sensitizing agents which overcome INSULIN RESISTANCE by activation of the peroxisome proliferator activated receptor gamma (PPAR-gamma). Glitazones
D051297 Sodium-Glucose Transporter 2 A sodium-glucose transporter that is expressed in the luminal membrane of the PROXIMAL KIDNEY TUBULES. SGLT2 Protein,SLC5A2 Protein,Sodium Glucose Transporter 2

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