Miscellaneous Drugs
Sarah Armstrong, Barry Clifton, Lionel Davis in Primary FRCA in a Box, 2019
The oral drugs used in diabetes are sulfonylureas, biguanides and other antidiabeticsSulfonylureas include first generation (e.g. tolbutamide) and second generation (e.g. glibenclamide, gliclazide, glipizide) drugs which increase insulin release from the pancreas. Cimetidine inhibits their metabolism increasing their effect. Thiazides, corticosteroids and phenothiazines antagonise their effectMetformin is the only biguanide available in the UK. It delays gut glucose uptake, increases peripheral insulin sensitivity and inhibits renal and hepatic gluconeogenesis. It may cause severe lactic acidosis especially in renal impairment or alcohol abusersAcarbose delays intestinal glucose absorption, pioglitazone (a thiazolidinedione) improves insulin sensitivity and meglitinides (e.g. repaglinide and metiglinide) increase insulin secretion by the pancreas
Gestational Diabetes
Emmanuel C. Opara, Sam Dagogo-Jack in Nutrition and Diabetes, 2019
Metformin, a biguanide that inhibits hepatic gluconeogenesis and glucose absorption and stimulates glucose uptake by the peripheral tissue, gained acceptance to be used in pregnancy after several studies demonstrated its safety. A large, randomized controlled trial (RCT) assigned 751 women with GDM to receive insulin or metformin. The composite outcome of perinatal morbidity, which included neonatal hypoglycemia, respiratory distress, phototherapy, birth trauma, prematurity and low APGAR scores, was noted to be similar in both groups; however, 46% of women who took metformin eventually required insulin (35). Another RCT of 47 women per arm evaluated glycemic control in women receiving metformin or insulin in GDM to identify factors predicting the need for supplemental insulin in those treated with metformin. Metformin was noted to provide adequate glycemic control with lower mean glucose levels, less weight gain, and lower frequency of neonatal hypoglycemia; however, 26% of women receiving metformin required supplemental insulin (36). A meta-analysis of six randomized clinical trials that included 1,420 patients suggested that metformin use in pregnancy did not significantly increase adverse maternal outcomes and neonatal outcomes. There was less weight gain and less rates of neonatal hypoglycemia; however, there was a higher incidence of premature births (37). Another meta-analysis including 2,509 patients found no difference when comparing metformin and insulin; however, metformin had a higher rate of preterm birth, with a risk ratio of 1.5 (38).
Information on level of drugs into breastmilk
Wendy Jones in Breastfeeding and Medication, 2018
Metformin produces anorexia, diarrhoea and taste disturbances but has been shown to reduce morbidity and mortality in Type 2 diabetes. Metformin is used when dietary modification alone has not produced glycaemic control. It is not associated with weight gain. Biguanides do not usually lower blood-glucose concentrations in patients without diabetes. In a study of seven breastfeeding women, concentrations of metformin in milk were found to be about a third of those in maternal plasma (Hale et al. 2002). Blood sample levels of metformin were undetectable in two babies, and at very low levels in the others. Similar results have been found in three other studies. There were no reported adverse effects on the babies in the studies (Gardiner et al. 2003; Briggs et al. 2005; Eyal et al. 2010) or in using it to treat polycystic ovary syndrome (PCOS) (Glueck et al. 2006).
Comparative efficacy and safety profile of once-weekly Semaglutide versus once-daily Sitagliptin as an add-on to metformin in patients with type 2 diabetes: a systematic review and meta-analysis
Published in Annals of Medicine, 2023
Tirath Patel, Fnu Nageeta, Rohab Sohail, Tooba Shaukat Butt, Shyamala Ganesan, Fnu Madhurita, Muhammad Ahmed, Mahrukh Zafar, Wirda Zafar, Mohammad Uzair Zaman, Giustino Varrassi, Mahima Khatri, Satesh Kumar
This meta-analysis comprised a total of 2401 participants, with 800 (33.3%) subjects assigned to the Semaglutide 0.5 mg group, 801 (33.4%) to the Semaglutide 1 mg group, and 800 (33.3%) to the Sitagliptin 100 mg group. The gender distribution of the participants showed that 1199 (49.9%) were male and 1096 (45.6%) were female. The average age of the participants was 55.4 ± 10.4 years. The mean HbA1C was 8.1 ± 0.9%, and the mean duration of diabetes was 7 ± 5.2 years. Most of the participants were overweight, with an average BMI of 28.6 ± 4. Prior to enrollment in the respective trials, 1690 out of 2401 (70.4%) participants were taking biguanides, while others were on medications such as sulphonylureas, thiazolidinediones, DPP-4 inhibitors, and alpha-glucosidase inhibitors. A detailed summary of the baseline characteristics of the participants can be found in Tables 1 and 2.
Metabolic and Metabolomic Effects of Metformin in Murine Model of Pulmonary Adenoma Formation
Published in Nutrition and Cancer, 2023
Andrew C. Elton, Vannesa Cedarstrom, Arman Quraishi, Beverly Wuertz, Kevin Murray, Todd W. Markowski, Donna Seabloom, Frank G. Ondrey
There has been significant interest in the use of type II diabetes agents in aerodigestive carcinoma prevention. There have been minimally five human clinical trials using either thiazolidinediones or biguanides alone or in combination (NCT00099021, NCT02917629, NCT00780234, NCT00951379, NCT05237960). These have not been definitive studies to go through a Phase III clinical trial; however, there are new federally funded projects with metformin or metformin and pioglitazone starting in 2023 for oral cancer prevention. In the present study, we sought to examine various chemoprevention diets on the effect of metformin on lung adenoma prevention. We are seeking additional insight into potential effects, including the metabolomic effects of both metformin and the diet, in aerodigestive chemoprevention. These may inform dosing, scheduling, and duration of treatment, and how diet may impact the chemopreventative effects of biguanides. Therefore, we tested the effect of metformin on both reduction of lung adenomas and potential metabolomic effects of this intervention. We also sought to examine whether different diets affected the adenoma reduction.
Do antidiabetic drugs prevent the transformation of Acanthamoeba trophozoite into cyst form?
Published in Pathogens and Global Health, 2022
Necati Ozpinar, Ulku Karaman, Hulya Ozpinar, Seker Dag
In comparison of the effects of metformin, acarbose and pioglitazone used in the study on A. castellanii trophozoites and cysts, it was observed that all three substances were statistically effective against cysts and trophozoites at a concentration of 0.75 mg/mL. Furthermore, it was determined that all concentrations of the three active substances included in the study significantly decreased the rate of cyst formation even at the end of the 7th day. In this context, it was determined that all three substances have amebicidal effects, and they significantly inhibit the transformation of A. castellanii trophozoites to cyst form. Despite treatment attempts, the encystment of these amoebae under stress is one of the main causes of resistance to many therapeutics. It is thought that these active substances, which are currently used as anti-diabetic, can be used in combination with other drugs in A. castellanii infections based on our study findings. Moreover, studies on the interaction of these active substances with other therapeutics (e.g. biguanides and diamidines) used in treatment and in vivo studies are needed.