Non-insulin therapies in addition to insulin in Type 1 DM treatment

2020 ◽  
Vol 134 (1) ◽  
pp. 54-62
Author(s):  
Andrea Llano ◽  
Gerard A McKay

Abstract Introduction Complications of Type 1 diabetes (T1DM) remain prevalent due to suboptimal glycaemic control despite advances in analogue insulin, its delivery and technological advances in glucose monitoring. Intensive insulin therapy is associated with hypoglycaemia and weight gain. Non–insulin-dependent glucose lowering strategies may provide a strategy in improving glycaemic control without hypoglycaemia and weight gain. Sources of data Research papers and reviews about adjunctive treatment with insulin in T1DM in the published literature. Areas of agreement Non–insulin-dependent strategies may be beneficial inT1DM particularly when there is insulin resistance, but the evidence for benefit at the current time is limited. Although there have been trials with various drugs as adjunctive therapy to insulin in T1DM currently in the UK, there is only one sodium glucose transport protein 2 (SGLT2) inhibitor with a marketing authorization for use in this indication. Areas of controversy Potential for harm with SGLT2 inhibitors in T1DM is a potential issue, particularly euglycaemic diabetic ketoacidosis. Clinical trials confirm that there is a risk albeit small, but emerging safety data have led to questions as to whether the risk of euglycaemic diabetic ketoacidosis is higher with the use of SGLT2 inhibitors in clinical practice. Growing points Patient education is paramount—the work being done in T1DM to ensure safe use of SGLT2 inhibitors may help improve safety in the prescribing of SGLT2 inhibitors in Type 2 diabetes. Areas timely for developing research There is a need for larger clinical trials with SGLT2 inhibitors in T1DM and real world studies to clarify safety.

2014 ◽  
Vol 10 (2) ◽  
pp. 117
Author(s):  
Rene A Oliveros ◽  
Son V Pham ◽  
Steven R Bailey ◽  
Robert J Chilton ◽  
◽  
...  

Currently available medications for the treatment of type 2 diabetes have limitations, and many patients do not achieve glycaemic control. Recently, a new approach has emerged using sodium glucose co-transporter 2 (SGLT2) inhibitors that decrease glucose reabsorption in the kidneys, increasing urinary glucose excretion. These agents offer the potential to improve glycaemic control independently of insulin pathways while avoiding hypoglycaemia. Two drugs of this class, canagliflozin and dapagliflozin, have been approved by the US Food and Drug Administration (FDA); another, empagliflozin, has been filed for regulatory approval and several others are in advanced development. These drugs have been shown to effectively reduce blood glucose, fasting plasma glucose and glycated haemoglobin (HbA1C) levels in phase III clinical trials when used as monotherapy and as add-on therapy to other diabetes medications, including insulin. Another advantage of the SGLT2 inhibitors over existing treatments is the improvement in cardiovascular risk factors, particularly in terms of reductions in blood pressure and body weight. SGLT2 inhibitors have been generally well tolerated. While more long-term safety data are required to elucidate the benefit–risk profile of SGLT2 inhibitors, the rationale for their use in type 2 diabetes therapy is strong.


2019 ◽  
Vol 14 (2) ◽  
pp. 87-93 ◽  
Author(s):  
Mahakpreet Singh ◽  
Ruchika Sharma ◽  
Anoop Kumar

Background:Recently, Food and Drug Administration (FDA) has approved sodium/ glucose co-transporter 2 (SGLT2) inhibitors for the treatment of diabetes mellitus. However, regarding adverse drug reactions (ADRs) of SGLT2 inhibitors in large group of population, very less information is available. Thus, we have tried to find out the risk profile of SGLT2 inhibitors. Materials and Methods: A total of 1,042 studies have been published from Nov. 2012-Nov. 2017 regarding SGLT2 inhibitors. After inclusion and exclusion criteria, 27 studies have been selected for the analysis of risk. Results and Discussion:The emerging evidence indicates various adverse drug reactions such as foot and toe amputation, cancer, diabetic ketoacidosis, bone fracture risk and urinary as well as mycotic genital infection. The causality assessment has shown a correlation between SGLT2 inhibitors and diabetic ketoacidosis and urinary tract infection. Conclusion:In conclusion, Marketing Authorization Holder (MAH) and Regulatory Authorities (RA) should monitor various adverse drug reactions such as diabetic ketoacidosis and urinary tract infection with the use of SGLT2 inhibitor.


2021 ◽  
Vol 21 (10) ◽  
pp. 5051-5056
Author(s):  
Jiao Wang ◽  
Lihai Zhang ◽  
Xianhe Wang ◽  
Jing Dong ◽  
Xiuhua Chen ◽  
...  

Type 1 diabetes is an insulin-dependent type of diabetes that is most common among children. Due to absolute deficiency of insulin in patients, diabetic ketoacidosis (DKA) can easily ensue. Insulin pump can simulate the physiological secretion of islet, but increases the risk of pain and infection in children due to its traumatic effect. This study aimed to analyze the application effect of nano-insulin pump in children with DKA. Children with DKA admitted to our hospital from May 2018 to May 2020 were included in this study and, according to the random number table method, they were divided into two groups, with each group containing 36 cases. The first group received traditional insulin pump infusion (IP), while the second group received nano-insulin pump infusion (NIP). It was found that the reduction of FBG and PBG in NIP group was greater than that in IP group. The recovery time of urine ketone, blood ketone, glucose, venous pH, and other clinical indicators in the NIP group were all lower than those in the IP group (P < 0.05). The length of hospital stay, insulin dosage, incidence of hypoglycemia, and infusion site infection rate in the NIP group were all lower than those in the IP group (P <0.05). The findings indicate that the application of nano-insulin pump in children with DKA had a significant effect and could quickly and obviously correct the levels of blood glucose and ketone body in children.


2021 ◽  
Author(s):  
Michael Colacci ◽  
John Fralick ◽  
Ayodele Odutayo ◽  
Michael Fralick

Importance: The risk of diabetic ketoacidosis (DKA) with sodium-glucose cotransporter-2 (SGLT2) inhibitors is unclear. Objective: To examine the risk of DKA with SGLT2 inhibitors in both observational studies and large clinical trials. Data Sources: Searches of PubMed, EMBASE and CENTRAL (inception to 15 April 2019) without language restrictions; conference proceedings; and reference lists. Study Selection: Randomized controlled trials and observational studies that quantified the rate of diabetic ketoacidosis with an SGLT2 inhibitor in comparison to another diabetes medication or placebo. Data Extraction and Synthesis: Two independent investigators abstracted study data and assessed the quality of evidence. Data were pooled using random effects models with the Hartung-Knapp-Sidik-Jonkman method. Main Outcome and Measures: Absolute event rates and hazard ratios for diabetic ketoacidosis were extracted from each study. Results: Seven randomized trials encompassing 42,375 participants and five cohort studies encompassing 318,636 participants were selected. Among the 7 randomized controlled trials, the absolute rate of DKA among patients randomized to an SGLT2 inhibitor ranged from 0.6 to 2.2 events per 1000 person years. Four randomized trials were included in the meta-analysis, and compared to placebo or comparator medication, SGLT2 inhibitors had a 2.4-fold higher risk of DKA (Relative Risk [RR] = 2.46 [95% CI, 1.16-5.21]; I2 = 0%; P = 0.54). Among the 5 observational studies, the absolute rate of DKA associated with SGLT2 inhibitor use ranged from 0.6 to 4.9 per 1000 person years and a 1.7-fold higher rate of DKA compared to another diabetes medication (RR = 1.74 [95% CI, 1.01-2.93]; I2 = 45%; P = 0.12). Conclusions and Relevance: In adults with type 2 diabetes, SGLT2 inhibitors increase the risk of DKA in both observational studies and large randomized clinical trials. Registration: CRD42019146855 Funding Source: None


2019 ◽  
Vol 71 (9) ◽  
pp. 1393-1399 ◽  
Author(s):  
Fei Huang ◽  
Fuwei Dai ◽  
Jianhua Bi ◽  
Lanxiang Hao ◽  
Chunlei Wang ◽  
...  

BJPsych Open ◽  
2017 ◽  
Vol 3 (3) ◽  
pp. 138-140 ◽  
Author(s):  
Alejandro Porras-Segovia ◽  
Amir Krivoy ◽  
Mark Horowitz ◽  
George Thomas ◽  
Mark Bolstridge ◽  
...  

Clozapine has proved to be an effective antipsychotic for the treatment of refractory schizophrenia – characterised by the persistence of symptoms despite optimal treatment trials with at least two different antipsychotics at adequate dose and duration – but its use is hampered by adverse effects. The development of clozapine-induced diabetes is commonly considered to arise as part of a metabolic syndrome, associated with weight gain, and thus evolves slowly. We present the case of an individual with refractory schizophrenia and metformin-controlled diabetes who developed rapid-onset insulin-dependent hyperglycaemia immediately after starting clozapine. Given the refractory nature of his illness, the decision was made to continue clozapine and manage the diabetes. This case supports the existence of a more direct mechanism by which clozapine alters glycaemic control, aside from the more routine slow development of a metabolic syndrome.


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