Simplifying Type 2 DM Care with Linagliptin: A Position Paper.

INTRODUCTION: The burden of type 2 diabetes mellitus (T2DM) is raising dramatically both internationally and in India. It is often observed that multiple therapies or combinations of different drugs are usually required to successfully control hyperglycemia in patients with T2DM. To facilitate effective control of glucose levels, many new agents have been developed over the past few years. MATERIALS AND METHODS: Multiple Advisory Board Meetings were conducted with 87 leading key opinion leaders (KOLs) from diabetes specialty PAN India to understand the simplicity aspect of linagliptin therapy in T2DM patients. DISCUSSION: Linagliptin is a xanthine-based, non-peptidomimetic, selective dipeptidyl peptidase 4 (DPP-4) inhibitor with a different pharmacological profile when compared to other DPP-4 inhibitors already available in India. It is known to decrease the risk of hypoglycemia compared to sulphonylurea (SU), is weight neutral, and no dose modification is required over a broad range of patient populations. This consensus paper discusses the clinical efficacy of DPP-4 inhibitors and linagliptin in T2DM. It also highlights the evidence for the safety of linagliptin in T2DM patients with renal impairment (RI), cardiovascular (CV) risk, and heart failure (HF). CONCLUSION: Linagliptin therapy is simplifying the management of T2DM with good efficacy and its use across a wide range of patients without any dose modification.

Overview of Clinical Trial Program and Applicability of Insulin Degludec/Insulin Aspart in Diabetes Management.

Insulin degludec/insulin aspart (IDegAsp) is the first soluble coformulation combining a long-acting insulin degludec (IDeg) and rapid-acting insulin aspart (IAsp). In patients with uncontrolled type 2 diabetes (T2DM) previously treated with insulins, IDegAsp twice daily effectively improves glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) levels with fewer hypoglycaemic episodes versus premix insulins. Further, insulin initiation with IDegAsp once daily provides superior long-term glycaemic control compared to insulin glargine with similar FPG and insulin doses, and numerically lower rates of overall and nocturnal hypoglycaemia. In patients with type 1 diabetes mellitus (T1DM), IDegAsp once daily and IAsp at remaining meals provides more convenient three injection regimen per day over conventional 4-5 injections based basal-bolus therapy. IDegAsp is an appropriate and reasonable option for intensifying insulin therapy in patients with T2DM and a relatively less complex treatment option for the management of T1DM.

Discharge Planning for People with Inpatient Hyperglycaemia: A Review on Pharmacological Management.

Inadequate glycaemic control post-discharge is the root cause of readmission in people with diabetes mellitus (DM) and is often linked to improper discharge planning (DP). A structured DP plays a crucial role in ensuring continuing home care and avoiding readmissions. DP should help patients in self-care and provide appropriate guidance to maintain optimal glycaemic control. There is a scarcity of reports and recommendations on the proper DP for people with DM on insulin therapy. The present review provides important consideration based on experts' opinions from the National Insulin and Incretin summit (NIIS), focusing on the effective treatment strategies at the time of discharge, especially for insulin therapy. A review of literature from PubMed and Embase was conducted. The consensus was derived, and recommendations were made on effective DP for patients with DM. Recommendations were drawn at the NIIS for post-discharge treatment for medical and surgical cases, stress-induced hyperglycaemia, elderly, pregnant women, and coronavirus disease 2019 (COVID-19) cases. The committee also recommended a comprehensive checklist to assist the physicians during discharge.

Clinical Effectiveness and Impact on Insulin Therapy Cost After Addition of Dapagliflozin to Patients with Uncontrolled Type 2 Diabetes.

INTRODUCTION: Dapagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, is a promising drug approved for the treatment of type 2 diabetes mellitus (T2DM). However, its cost is an obstacle for use in developing countries like India. Thus, we aimed to analyse the impact on the cost of insulin therapy after adding dapagliflozin for patients using insulin in real-world clinical practice. METHODS: This retrospective chart review study included patients with uncontrolled T2DM previously on maximum doses of OADs and insulin therapy, initiated on dapagliflozin. Parameters measured were: HbA1c, changes in weight and insulin dosage, frequency and cost, at baseline and after 3 months of adding dapagliflozin 10 mg. Hospital records of patients attending the diabetes outpatient departments at the study centres were scrutinised to identify eligible patients. A treat-to-target approach was used to make changes in the insulin dosages and regimen. The cost of insulin was calculated based on the total daily dose, cost per unit based on the formulation and insulin delivery device. Statistical analysis included descriptive and inferential methods. RESULTS: Overall, 70 patients meeting the inclusion criteria were included in the study. The mean age of patients and duration of T2DM were 52.6 ± 10 and 12 ± 5 years respectively. The mean reduction in HbA1c and weight was 2.1 ± 1% (p < 0.01) and 2.4 ± 1 kg (p < 0.01) respectively. Genital mycotic infections were reported in two (2.8%) patients. The mean reduction in the total daily dose of insulin was 9.5 ± 6 units. A significant reduction in the daily insulin requirement (19.87%, p < 0.01) was observed. The cost of insulin decreased by 22.3% or 17.8 ± 15 INR per day ($0.27 ± 0.22 per day) and the frequency of insulin shots administered per day decreased significantly (p < 0.01). In 12.8% and 2.8% of patients the frequency of administration of insulin decreased by one and two injections per day respectively. CONCLUSIONS: Reduction in HbA1c and body weight along with minimal side effects was observed. Addition of dapagliflozin reduced the insulin daily dose requirement and cost of insulin therapy in these patients. FUNDING: Diacon Hospital, Bangalore, India.

Liraglutide effect and action in diabetes-In (LEAD-In): A prospective observational study assessing safety and effectiveness of liraglutide in patients with type 2 diabetes mellitus treated under routine clinical practice conditions in India.

BACKGROUND: This 26-week, open-label observational study assessed the incidence and type of adverse events (AEs) associated with liraglutide use according to the standard clinical practice settings and the local label in India. MATERIALS AND METHODS: A total of 1416 adults with type 2 diabetes (T2D) treated with liraglutide in 125 sites across India were included in the study. Participants were newly diagnosed or already receiving antidiabetic medications. Safety and efficacy data were collected at baseline and at approximately weeks 13 and 26. The primary outcome was incidence and type of AEs while using liraglutide, with events classified by Medical Dictionary for Regulatory Activities system organ class and preferred term. The secondary objective was to assess other clinical parameters related to effective T2D management. RESULTS: Twenty AEs, predominately gastrointestinal, were reported in 1.3% of the study population in scheduled visits up to week 26. No serious AEs, including death, were reported. Hypoglycemic episodes were reported in 7.3% of participants at baseline and 0.7% at week 26. No major hypoglycemic events were reported up to week 26 (baseline: 0.4%). Glycated hemoglobin was reduced from baseline (8.8 ± 1.3%) to week 26 by 1.6 ± 1.1% (P < 0.0001); significant improvements in fasting blood glucose, and 2-h postprandial blood glucose (post-breakfast, -lunch, and -dinner) were also observed. Mean body weight decreased by 8.1 ± 6.5 kg from baseline (92.5 ± 14.6 kg; P < 0.0001). CONCLUSIONS: From the number of AEs reported, it is suggested that liraglutide was well tolerated in subjects with T2D treated under standard clinical practice conditions in India. Liraglutide was effective, and no new safety concerns were identified.

Switching from basal or basal-bolus insulin to biphasic insulin aspart 30: Results from the Indian cohort of the A1 chieve study.

AIM: To determine the safety and efficacy of biphasic insulin aspart 30 (BIAsp 30) therapy in the Indian patients with type 2 diabetes previously on basal or basal-bolus insulin therapies. MATERIALS AND METHODS: Patients switching from insulin glargine, neutral protamine Hagedorn (NPH) insulin, or basal-bolus insulin to BIAsp 30 in the Indian cohort of the A1 chieve study were included. Safety and efficacy of treatment was evaluated over 24 weeks. RESULTS: A total of 422 patients (pre-study basal-bolus insulin, 49; NPH insulin, 157; insulin glargine, 216) switched to BIAsp 30. Pre-study insulin doses were 0.61 ± 0.26 U/kg, 0.34 ± 0.2 U/kg and 0.40 ± 0.21 U/kg and the mean week 24 BIAsp 30 doses were 0.50 ± 0.21 U/kg, 0.35 ± 0.15 U/kg and 0.42 ± 0.16 U/kg in the prior basal-bolus insulin, NPH insulin and insulin glargine groups, respectively. No serious adverse drug reactions, major or nocturnal hypoglycemia were reported. The proportion of patients experiencing overall hypoglycemia was significantly lower from baseline (5.6%) to week 24 (1.0%) in the pre-study insulin-glargine group and appeared to be lower in pre-study NPH insulin and basal-bolus insulin groups. Glycemic control improved significantly from baseline week 24 in the pre-study NPH insulin and insulin-glargine groups (P < 0.001), while it appeared to improve in the pre-study basal-bolus group. Quality of life was positively impacted after 24 weeks in all 3 groups. CONCLUSION: The switch from basal or basal-bolus insulin to BIAsp 30 was safe, well tolerated and improved the glycemic control in this Indian cohort.

Importance of achieving the composite endpoints in diabetes.

Well-conducted randomized controlled trials are instrumental in providing vital data on safety and efficacy of new molecules under consideration for approval. However acquiring such data involves huge cost and focused scientific endeavor. Selection and reporting of endpoints of a therapy is essential to assess the effect(s) of an intervention on overall disease control and guidelines have suggested the use of composite endpoint (CEP) in clinical trial design over individual endpoints to demonstrate the compound effect. Composite endpoints have been preferred for their ability to assess the net clinical benefit of an intervention, avoid misinterpretation associated with competing risks, avoid the challenge of using a single outcome to validate the study objectives and reduce the sample size requirements in trials on patients treated for diabetes. Concerns for misinterpretation or difficulty in interpretation of trial results involving CEPs arise when differences in the components with respect to either clinical importance or event rates, or magnitude of treatment effect exist and when there's a possibility of biases due to competing risk. Suggestions for construction of composite endpoints and reporting the results of trials involving CEPs have been presented to improve the interpretations of overall effect of new interventions.

Thyroid disorders in pregnancy.

Thyroid disorders are common in pregnancy and the most common disorder is subclinical hypothyroidism. Due to the complex hormonal changes during pregnancy, it is important to remember that thyroxine requirements are higher in pregnancy. According to recent American Thyroid Association (ATA) guidelines, the recommended reference ranges for TSH are 0.1 to 2.5 mIU/L in the first trimester, 0.2 to 3.0 mIU/L in the second trimester, and 0.3 to 3.0 mIU/L in the third trimester. Maternal hypothyroidism is an easily treatable condition that has been associated with increased risk of low birth weight, fetal distress, and impaired neuropsychological development. Hyperthyroidism in pregnancy is less common as conception is a problem. Majority of them are due to Graves' disease, though gestational hyperthyroidism is to be excluded. Preferred drug is propylthiouracil (PTU) with the target to maintain free T4 in upper normal range. Doses can be reduced in third trimester due to the immune-suppressant effects of pregnancy. Early and effective treatment of thyroid disorder ensures a safe pregnancy with minimal maternal and neonatal complications.