Sodium-Glucose Cotransporters as Potential Therapeutic Targets in Patients With Type 1 Diabetes Mellitus: An Update on Phase 3 Clinical Trial Data

2019 ◽  
Vol 53 (12) ◽  
pp. 1227-1237 ◽  
Author(s):  
Kajal Patel ◽  
Antonia Carbone
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Glucose Transporter ◽  
Trial Data ◽  
Mitigation Strategies ◽  
Phase 3 ◽  
Glucose Transporter 2 ◽  
Increased Risk

Objective: To review phase 3 trials of sodium-glucose cotransporter (SGLT) inhibitors in type 1 diabetes mellitus (T1DM) patients. Data Sources: A literature search of Ovid MEDLINE databases (1946 through May 17, 2019) limited to English-language human clinical trials was conducted using the following terms: sodium-glucose transporter 2 inhibitors, canagliflozin, dapagliflozin, empagliflozin, sotagliflozin, ertugliflozin, ipragliflozin, or remogliflozin combined with type 1 diabetes mellitus. Results were verified via Google Scholar and clinicaltrials.gov. Study Selection and Data Extraction: Articles were included if they were phase 3 trials in adults with T1DM. Data Synthesis: Phase 3 trials are available for dapagliflozin, empagliflozin, and sotagliflozin. All 3 drugs demonstrated statistically significant reductions in hemoglobin A1C, weight, and total daily insulin dose without an increased risk of hypoglycemia in up to 52 weeks of therapy. The incidence of diabetic ketoacidosis (DKA) was higher in patients on a SGLT inhibitor at all doses, with the exception of empagliflozin 2.5 mg (0.8% vs 1.2% with placebo). Relevance to Patient Care and Clinical Practice: SGLT inhibitors are potential adjuncts to insulin in T1DM patients, providing clinically meaningful benefits. Regulatory bodies have either approved or are reviewing these agents for use in T1DM. Clinicians should be familiar with the DKA risk associated with SGLT inhibitors and utilize DKA risk-mitigation strategies. Empagliflozin 2.5 mg warrants additional investigation given its efficacy without an increased incidence of DKA. Conclusions: Phase 3 trial data of SGLT inhibitors provide evidence for sustained efficacy in T1DM patients. Appropriate patient selection for therapy and routine monitoring are essential to minimize associated risks.

SGLT-2 Inhibitors: Is There a Role in Type 1 Diabetes Mellitus Management?

2017 ◽  
Vol 51 (9) ◽  
pp. 791-796 ◽  
Author(s):  
Nabila Ahmed-Sarwar ◽  
Angela K. Nagel ◽  
Samantha Leistman ◽  
Kevin Heacock
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
English Language ◽  
Glucose Transporter ◽  
Small Sample ◽  
Publication Type ◽  
Glucose Transporter 2 ◽  
Mesh Terms

Objective: The purpose of this review is to identify and evaluate disease management of patients with type 1 diabetes mellitus (T1DM) who were treated with a sodium-glucose cotransporter 2 (SGLT-2) inhibitor as an adjunct to insulin therapy. Data Sources: A PubMed (1969 to March 2017) and Ovid (1946 to March 2017) search was performed for articles published utilizing the following MESH terms: canagliflozin, empagliflozin, dapagliflozin, type 1 diabetes mellitus, insulin dependent diabetes, insulin, sodium-glucose transporter 2. There were no limitations placed on publication type. Study Selection and Data Extraction: All English-language articles were evaluated for association of SGLT-2 inhibitors and type 1 diabetes. Further studies were identified by review of pertinent manuscript bibliographies. Data Synthesis: All 3 SGLT-2 inhibitors, when combined with insulin, resulted in an overall reduction of hemoglobin A1C (up to 0.49%), lower total daily insulin doses, and a reduction in weight (up to 2.7 kg). The combination therapy of insulin and SGLT-2 inhibitors also resulted in a lower incidence of hypoglycemia. Study duration varied from 2 to 18 weeks. Conclusion: A review of the identified literature indicated that there is a potential role for the combination of SGLT-2 inhibitors with insulin in T1DM for improving glycemic control without increasing the risk of hypoglycemia. The short duration and small sample sizes limit the ability to fully evaluate the incidences of diabetic ketoacidosis and urogenital infections. The risks associated with this combination of medications require further evaluation.

scholarly journals Pregnancy and delivery in a patient with a 40-year history of type 1 diabetes mellitus and antiphospholipid syndrome

2018 ◽  
Vol 67 (6) ◽  
pp. 93-99
Author(s):  
Roman V. Kapustin ◽  
Natalia V. Borovik ◽  
Ekaterina V. Musina ◽  
Olga N. Arzhanova ◽  
Maria I. Yarmolinskaya ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Antiphospholipid Syndrome ◽  
Perinatal Outcomes ◽  
Increased Risk ◽  
Pregnancy And Delivery ◽  
Perinatal Center ◽  
History Of

Type 1 diabetes mellitus is a condition associated with an increased risk of adverse perinatal outcomes such as spontaneous abortions, preterm birth, placental insufficiency, congenital malformations, and perinatal mortality. Diabetes mellitus combined with cardiovascular diseases in women during pregnancy often leads to hypertensive disorders and pre-eclampsia. The severity of the microvascular diabetic complications and frequency of hypoglycemic episodes, particularly in early pregnancy, are related to the risk of pre-eclampsia. We report the case of pregnancy and delivery of a live newborn in a 42-year-old woman with type 1 diabetes mellitus, pre-existing hypertension, heritable thrombophilia, and antiphospholipid syndrome. She had a 40-year history of type 1 diabetes mellitus with well-controlled diabetic nephropathy and retinopathy. The woman had been receiving continuous subcutaneous insulin therapy for the last five years, which allowed maintaining an appropriate glycemic control during pregnancy. Multidisciplinary supervision of course of pregnancy was carried out from the pre-gravidity stage until delivery and postpartum. In spite of the severe pre-eclampsia and preterm delivery by cesarean section at 36 weeks, she and newborn could avoid the intensive unit care and discharge from perinatal center without any complications.

scholarly journals Risk of Urticaria in Children with Type 1 Diabetes Mellitus: A Nationwide Cohort Study

2019 ◽  
Vol 17 (1) ◽  
pp. 176
Author(s):  
Shih-Yi Lin ◽  
Cheng-Li Lin ◽  
Cheng-Chieh Lin ◽  
Wu-Huei Hsu ◽  
Chung-Y. Hsu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Hazard Ratio ◽  
Control Group ◽  
Case Group ◽  
Research Database ◽  
Increased Risk ◽  
Type 1 Dm

Type 1 diabetes mellitus (T1DM) has been linked to many autoimmune problems. The association between T1DM and urticaria warrants investigation. Data were extracted from the National Health Insurance Research Database (NHIRD) of Taiwan. Participants with T1DM were recruited as the case group, and that group was matched by sex and age at a ratio of 1:4 to the control group comprising those without T1DM. The study period was 1998–2011. All participants were followed up to the diagnosis of urticaria, withdrawal from the insurance program, death, or the end of the study. A multivariable Cox proportional hazard model was used to calculate the adjusted and crude hazard ratios for urticaria. A total of 5895 participants (1179 in the case group and 4716 in the control group) were followed up in the study. The total incidence rate of urticaria in patients with type 1 DM was 26.6 per 1000 person-years, and that in controls was 6.85 per 1000 person-years. Compared with the control group, the hazard ratio of urticaria in the case group was 2.84 (95% CI = 2.27–3.56). Compared with age-matched participants without T1DM, patients with type 1 DM aged <18 years had a 3.62-fold higher risk of urticaria (95% CI = 2.85–4.59). The hazard ratio in patients with an adjusted Diabetes Complications Severity Index (aDCSI) score of 1.01–2.00 per year was 2.57 (95% CI = 1.18–5.57), and that in patients with an aDCSI score of >2.00 per year was 4.47 (95% CI = 2.68–7.47). T1DM patients aged <18 years had an increased risk of urticaria, but a similar phenomenon was not observed among T1DM patients older than 18 years.

Teplizumab for Treatment of Type 1 Diabetes Mellitus

2012 ◽  
Vol 46 (10) ◽  
pp. 1405-1412 ◽  
Author(s):  
Jessica W Skelley ◽  
Lindsey K Elmore ◽  
Jeffrey A Kyle
Keyword(s):  
Diabetes Mellitus ◽  
Monoclonal Antibody ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Human Monoclonal Antibody ◽  
Clinical Trial Data ◽  
Data Sources ◽  
Β Cells ◽  
Phase 3

Objective: To review the pharmacology, pharmacokinetics, safety, and efficacy of teplizumab and evaluate relevant clinical trial data. Data Sources: Searches of MEDLINE, International Pharmaceutical Abstracts, ClinicalTrials.gov, American Diabetes Association scientific posters, and Google Scholar (1966-May 2012) were conducted using the key words teplizumab. anti-CD3 monoclonal antibody, MGA031, and hOKT3γ1 (Ala-Ala). Searches were limited to articles published in English. Study Selection and Data Extraction: Clinical trials evaluating teplizumab for type 1 diabetes mellitus (T1DM) published in English were selected from the data sources. All published relevant abstracts were included. References cited in identified articles were used for additional citations. Data Synthesis: T1DM accounts for up to 10% of all cases of diabetes mellitus, T1DM is characterized as a chronic and progressive autoimmune disease leading to the destruction of insulin-producing β-cells of the pancreas. Teplizumab is a humanized Fc-mutated anti-CD3 monoclonal antibody that alters the function of the T-lymphocytes that mediate the destruction of the insulin-producing β-cells. While clinical data are limited, both Phase 2 and Phase 3 studies have demonstrated preserved C-peptide response as a measure of insulin production, decreased exogenous insulin use, and improved grycemic control following a 12- to 14-day teplizumab infusion in patients diagnosed with T1DM within the previous 6 weeks. However, 1 Phase 3 trial tailed to find the same benefits in those diagnosed with T1DM within the previous 12 weeks when a lower cumulative teplizumab dose was used. Initial studies indicated that teplizumab is well tolerated, with a self-limiting rash as the most commonly reported adverse effect. Conclusions: Teplizumab is an anti-CD3 human monoclonal antibody with promising activity in treatment of patients with T1DM, Results from Phase 3 trials are needed to further determine safety, efficacy, and dosing frequency.

scholarly journals An exploration of Glo-3A antibody levels in children at increased risk for type 1 diabetes mellitus

2009 ◽  
Vol 10 (8) ◽  
pp. 563-572 ◽  
Author(s):  
M Simpson ◽  
M Mojibian ◽  
K Barriga ◽  
FW Scott ◽  
A Fasano ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Increased Risk ◽  
Antibody Levels
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