Sodium-Glucose Cotransporter-2 (SGLT-2) Inhibitors and Genital Infections in Patients With Diabetic Mellitus and Concomitant Coronary Artery Disease: A Single-Center Experience.

Objective To investigate the incidence of genital infection due to the use of sodium-glucose cotransporter-2 (SGLT-2) inhibitors in patients with type 2 diabetes mellitus (T2DM) concomitant coronary artery diseases (CAD). Methods A single-center, physician-initiated study was conducted at a tertiary-care center in India. The study enrolled patients with T2DM who were taking SGLT-2 inhibitors for at least two months and divided them into two groups: patients with concomitant CAD as the case group and without CAD as the control group. Demographic data and medical history of patients were documented using a standard questionnaire. Itching and swelling were the signs used for the diagnosis of genital infection. Results A total of 270 consecutive patients with T2DM were enrolled and divided into two groups: 48 patients with CAD as the case group and 222 patients without CAD as the control group. The mean age of patients with CAD was 63.27±7.53 years and without CAD was 58.32±14.89 years. The mean HbA1C levels were 8.40±1.71% in the case group and 8.60±7.20% in the control group. A total of 14.6% of patients with CAD and 12.6% of patients without CAD were found to have genital infections (p=0.712). SGLT-2 inhibitors were stopped in only six patients who had genital infections and all the patients were managed using anti-fungal cream and via maintenance of proper hygiene. The overall incidence of genital infection was about 12.96%, of which only 2.7% required discontinuation of this crucial therapy. Conclusion In conclusion, the incidence of genital infection with the use of SGLT-2 inhibitors is similar among patients with T2DM with concomitant CAD and without CAD. The measures to prevent genital infection should be strongly emphasized. However, larger, well-designed studies are required to validate the current findings.

Sodium-glucose Cotransporter-2 Inhibitors in Primary and Secondary Prevention of Cardiovascular and Renal Outcomes in Patients with Type 2 Diabetes Mellitus: A Meta-analysis.

BACKGROUND: The available evidence was systematically reviewed to evaluate the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i) on cardiovascular (CV) and renal outcomes in people with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD) or multiple risk factors (MRF), with or without heart failure (HF), and per estimated glomerular filtration rate (eGFR) rate at baseline. METHODS: We comprehensively searched three electronic databases to retrieve publications up to 30th November 2019, which were screened for inclusion. The data extracted for the outcomes according to baseline ASCVD, HF, and eGFR levels were meta-analyzed using fixed effects model. RESULTS: Of the 735 screened citations, 15 primary and secondary publications from five CV or renal outcome trials were included. SGLT2is reduced the risk of CV death or hospitalization for HF (HHF), HHF alone, and composite renal-specific outcome, irrespective of ASCVD and HF at baseline. The three-point major adverse cardiovascular events (3P-MACE) risk was reduced by 14% (p<0.001) in patients with ASCVD and by 10% (p = 0.018) in those without baseline HF compared with their counterparts. SGLT2is significantly reduced the risk of MACE (18%) in patients with mild kidney dysfunction (eGFR within the range of 60-<90 mL/min/1.73 m2 and <60 mL/min/1.73 m2 ). CONCLUSION: SGLT2is are effective for both secondary and primary prevention of composite CV outcomes, and secondary prevention of MACE. The upcoming evidence may strengthen the primary prevention benefits of SGLT2is.

One-year safety and effectiveness of insulin degludec in patients with diabetes mellitus in routine clinical practice in India-TRUST (Tresiba real-world use study).

Objective: This post-authorization safety study (PASS) was conducted to evaluate the long-term safety and effectiveness of insulin degludec in patients with diabetes mellitus (DM) requiring insulin therapy in routine clinical practice in India. Methods: Data on glycated hemoglobin (HbA1c) and adverse events (AEs) were collected up to 12 months after insulin degludec initiation. Results: A total of 1057 adult patients with DM were enrolled, including 60.07% males with the mean duration of 22.2 ± 21.90 years with type 1 DM and 10.1 ± 7.37 years with type 2 DM and the mean HbA1c of 9.6 ± 1.9%. Insulin degludec was prescribed to improve HbA1c and fasting plasma glucose (FPG). Insulin degludec daily dose was increased from 14.8 ± 8.0 U to 18.0 ± 9.46 U over 12 months resulting in a significant decrease of HbA1c by 1.8 ± 1.68% compared with baseline. There were 84 events of confirmed hypoglycemia in 51 patients during the 12-month follow-up period, and 44 AEs were reported in 2.6% of patients, of which 2 AEs were serious and unrelated to the drug. Conclusion: Insulin degludec is well tolerated in patients with DM. It improves glycemic control with reduced HbA1c, FPG, and postprandial glucose, with a low risk of hypoglycemia.

Humoral antibody kinetics with ChAdOx1-nCOV (Covishield™) and BBV-152 (Covaxin™) vaccine among Indian Healthcare workers: A 6-month longitudinal cross-sectional Coronavirus Vaccine-induced antibody titre (COVAT) study.

BACKGROUND AND AIMS: There is limited data available on longitudinal humoral antibody dynamics following two doses of ChAdOx1-nCOV (Covishield™) and BBV-152 (Covaxin™) vaccine against SARS-CoV-2 among Indians. METHODS: We conducted a 6-month longitudinal study in vaccinated healthcare workers by serially measuring quantitative anti-spike antibody at 3-weeks, 3-months and 6-months after the completion of second dose. Geometric mean titer (GMT) and linear mixed models were used to assess the dynamics of antibody levels at 6 months. RESULTS: Of the 481 participants, GMT of anti-spike antibody decreased by 56% at 6-months regardless of age, gender, blood group, body-mass index and comorbidities in 360 SARS-CoV-2 naive individuals but significantly more in hypertensives. Participants with past infection had significantly higher GMT at all time points compared to the naive individuals. Among SARS-CoV-2 naive cohorts, a significantly higher GMT was noted amongst the Covishield recipients at all time points, but there was a 44% decline in GMT at 6-month compared to the peak titer period. Decline in GMT was insignificant (8%) in Covaxin recipients at 6-month despite a lower GMT at all time points vs. Covishield. There was 5.6-fold decrease in seropositivity rate at 6-month with both vaccines. Participants with type 2 diabetes mellitus have a lower seropositivity rate at all the time points. Seropositivity rate was significantly higher with Covishield vs. Covaxin at all time points except at 6-month where Covaxin recipients had a higher seropositivity rate but no difference noted in propensity-matched analysis. CONCLUSIONS: There is waning humoral antibody response following two doses of either vaccine at six months. Covishield recipients had a higher anti-spike antibody GMT compared with Covaxin at all-time points, however a significant decline in antibody titers was seen with Covishield but not with Covaxin at 6-months.

Antibody response after first and second-dose of ChAdOx1-nCOV (CovishieldTM®) and BBV-152 (CovaxinTM®) among health care workers in India: The final results of cross-sectional coronavirus vaccine-induced antibody titre (COVAT) study.

BACKGROUND: We assessed the humoral immune response of both ChAdOx1-nCOV (CovishieldTM) and BBV-152 (CovaxinTM) vaccines in Indian health care workers (HCW). METHODS: A Pan-India, Cross-sectional, Coronavirus Vaccine-induced Antibody Titre (COVAT) study was conducted that measured SARS-CoV-2 anti-spike binding antibody quantitatively, 21 days or more after the first and second dose of two vaccines in both severe acute respiratory syndrome (SARS-CoV-2) naïve and recovered HCW. Primary aim was to analyze antibody response (seropositivity rate, Geometric Mean Titre [GMT] and 95% Confidence Interval [CI]) following each dose of both vaccines and its correlation to age, sex, blood group, body mass index (BMI) and comorbidities. Here we report the results of anti-spike antibody response after first and two completed doses. RESULTS: Among the 515 HCW (305 Male, 210 Female) who took two doses of both vaccines, 95.0% showed seropositivity to anti-spike antibody. However, both seropositivity rate and GMT (95% CI) of anti-spike antibody was significantly higher in Covishield vs. Covaxin recipients (98.1 vs. 80.0%; 129.3 vs. 48.3 AU/mL; both p < 0.001). This difference persisted in 457 SARS-CoV-2 naïve and propensity-matched (age, sex and BMI) analysis of 116 participants. Age > 60-years, males, people with any comorbidities, and history of hypertension (HTN) had a significantly less anti-spike antibody GMT compared to age ≤ 60 years, females, no comorbidities and no HTN respectively, after the completion of two doses of either vaccine. Gender, presence of comorbidities, and vaccine type were independent predictors of antibody seropositivity rate and anti-spike antibody titre levels in multiple logistic and log transformed linear regression analysis. Both vaccine recipients had similar solicited mild to moderate adverse events and none had severe or unsolicited side effects. CONCLUSIONS: Both vaccines elicited good immune response after two doses, although seropositivity rates and GMT of anti-spike antibody titre was significantly higher in Covishield compared to Covaxin recipients.

COVID-19 associated mucormycosis: A Descriptive Multisite Study from India.

BACKGROUND AND AIMS: Mucormycosis is an invasive fungal infection and carries a significant morbidity and mortality. A number of cases of mucormycosis have been reported in association with COVID-19. In this study, a consortium of clinicians from various parts of India studied clinical profile of COVID-19 associated mucormycosis (CAM) and this analysis is presented here. METHODS: Investigators from multiple sites in India were involved in this study. Clinical details included the treatment and severity of COVID-19, associated morbidities, as well as the diagnosis, treatment and prognosis of mucormycosis. These data were collected using google spreadsheet at one centre. Descriptive analysis was done. RESULTS: There were 115 patients with CAM. Importantly, all patients had received corticosteroids. Diabetes was present in 85.2% of patients and 13.9% of patients had newly detected diabetes. The most common site of involvement was rhino-orbital. Mortality occurred in 25 (21.7%) patients. On logistic regression analysis, CT scan-based score for severity of lung involvement was associated with mortality. CONCLUSION: Universal administration of corticosteroids in our patients is notable. A large majority of patients had diabetes, while mortality was seen in ∼1/5th of patients, lower as compared to recently published data.

Suboptimal glycemic control among subjects with diabetes mellitus in India: a subset analysis of cross-sectional wave-7 (2016) data from the International Diabetes Management Practices Study (IDMPS).

OBJECTIVE: To assess the real-world management practices of subjects with type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM) in India. METHODS: This cross-sectional study was conducted between 7 March 2016 and 15 May 2016 in India as part of the seventh wave (2016) of the International Diabetes Management Practices Study (IDMPS). Adult subjects with T1DM or T2DM visiting physicians during a 2-week recruitment period were included. RESULTS: A total of 55 physicians included 539 subjects who met eligibility criteria. Of 495 subjects with T2DM, 303 were treated with oral glucose lowering drugs (OGLDs) only, 158 were treated with OGLD + insulin, and 27 received insulin only. Among 44 subjects with T1DM receiving insulin, 13 (29.5%) were also treated with OGLD therapy. The most commonly used insulin regimens were basal alone (69/184; 37.5%) and premixed alone (63/184; 34.2%) in subjects with T2DM, and basal + prandial insulin (24/44; 54.5%) in subjects with T1DM. Proportions of subjects achieving glycemic targets were low [glycated haemoglobin (HbA1c) <7%: T1DM = 7.3% (3/44), T2DM = 25.2% (106/495); as targeted by the treating physician: T1DM = 31.8% (14/44), T2DM = 32.1% (59/185); global target: T1DM = 4.8% (2/42) and T2DM = 1.7% (8/482)]. In subjects with T2DM, HbA1c <7% was noted in 11/22 subjects receiving insulin only and 76/260 receiving only OGLDs. Lack of experience in self-managing insulin dosing, poor diabetes education and failure to titrate insulin dosages were the main reasons for non-achievement of glycemic targets. CONCLUSION: Timely insulinization, education and empowerment of people with diabetes may help improve glycemic control in India.

Consensus on Choice of Insulin Pen Devices in Routine Clinical Practice in India.

Although insulin delivery devices are widely used by the patients, there is a paucity of published guidelines to help professionals manage their patients in insulin therapies. To provide simple and easily implementable guidelines to health care physicians on the choice of insulin delivery devices in routine clinical practice, experts in diabetes gathered together and discussed the recommendations at the National insulin Summit 2018. An ideal insulin delivery device should accurately deliver the prescribed dose of insulin and be easy to use. Recommendations are: (1) insulin should be initiated by using an insulin device if the patient seems to discontinue insulin therapy. (2) Pen devices offer accurate dosing than a syringe and vial and are associated with cost savings in the long term. (3) Switching over from syringes and vial to disposable pen devices improves adherence. (4) FlexPen® offers better accuracy, and it requires lower dose force and injection force than SoloStar® and KwikPen® (5). Durable delivery pens such as NovoPen® 4 maintain accuracy and low dose force compared with vials and syringes. (6) One pen should be used by only one patient. (7) Regular counseling on the proper use of the pen device is required regularly. This consensus-based recommendation is a useful reference tool for health care practitioners to initiate insulin therapy in patients with diabetes by using the appropriate insulin pen device.

Adherence and Swallowing Experience with a Modified, Smaller-sized Tablet Formulation of Metformin and Glimepiride (SR) in Indian Patients with Type 2 Diabetes Mellitus.

BACKGROUND: This study evaluated the adherence and swallowing experience with novel oval-shaped, compact-sized metformin (500 mg/1000 mg)-glimepiride (1mg/2mg) combination, sustained-release tablet (Gluformin G1/Gluformin G2 SR; GM-new-SR) in Indian patients with T2DM, previously treated with conventional metformin-glimepiride combination tablet. METHODS: Patients' adherence, swallowing experience, and satisfaction were assessed at baseline and month-3 by Adherence to Refills and Medication Scale (ARMS12; adherent: ARMS12 score=12; nonadherent: ARMS12 score >12) and questionnaire based 5-point Likert scale, respectively. Safety was also assessed. RESULTS: Of 1550 patients enrolled, 1547 (99.8%) completed the study. After 3 months of switching to GM-new-SR tablets, adherence rate increased from 4.38% to 91.1%, with concurrent reduction in mean ARMS-12 score by 6.3±4.36 (p<0.0001). Compared to baseline, all glycemic indices, HbA1c, PPG, and FPG, significantly improved (p<0.0001) in the overall population. Reduction in HbA1c levels was significant only in patients who were adherent to therapy as opposed to nonadherent patients (7.8±1.74 to 7.1±0.85, p<0.0001 vs. 7.7±1.39 to 6.7±0.77, p=0.4276). Most patients attributed ease of swallowing of GM-new-SR tablets to its modified shape (95.5%) and size (94.9%). Most patients (90.4%) were satisfied with the new tablet formulation. Size of the tablet was the most common reason for patients' nonadherence with conventional tablets, which was reported to be less frequent with GM-new-SR tablets (2.5% vs 53.4%). CONCLUSION: Treatment with GM-new-SR tablets significantly increased adherence and was associated with improvement in glycemic indices, which could be attributed to the compact shape and size of the new tablet formulation.

Adherence, satisfaction, and experience with metformin 500 mg prolonged release formulation in Indian patients with type 2 diabetes mellitus: a postmarketing observational study.

PURPOSE: The aim of this study was to understand patient adherence, satisfaction, and experience with the smaller sized metformin 500 mg prolonged release (PR) tablet that has been manufactured with the help of technological advancement (Gluformin I 500 mg), in comparison with metformin 500 mg extended-release (ER) tablet, in patients with type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS: In this postmarketing observational study, T2DM patients who were on a stable dose of metformin 500 mg PR tablet for at least 1 month and had previously received metformin 500 mg ER tablet were recruited from 50 sites in India. The medication adherence and patients' experience, satisfaction, and perception with metformin 500 mg PR tablets were compared with metformin 500 mg ER tablets. The patients' experience was determined based on the external appearance of tablet, ease of swallowing, the presence of gastrointestinal discomfort, and ghost pill effect. RESULTS: A total of 1,000 patients were enrolled. The majority had medium adherence to metformin 500 mg PR tablet (54%) and did not report swallowing difficulties (66.2%) due to its small size (64.4%) and oval shape (64.3%). The PR formulation of metformin was more acceptable than ER formulation due to no aftertaste (63%). The ghost pill effect was reported in 0.7% of patients with metformin 500 mg PR tablet against 8.5% with ER tablet. More than 60% of patients were "comfortable" (67.9%), had "much effect on their well-being" (61.8%), and were "satisfied" (69%) with metformin 500 mg PR tablet compared with ER tablet. Patient's dissatisfaction (42.7%) and taste (24.9%) were the common reasons cited by physicians and patients, respectively, for changing the treatment from metformin 500 mg ER to metformin 500 mg PR formulation. A total of 10 adverse events (nonserious) were reported, and all of them were resolved. CONCLUSION: The technologically advanced formulation of metformin 500 mg PR tablets is more effective than that of metformin 500 mg ER tablets in improving adherence, compliance, satisfaction, and perception to medication in Indian patients with T2DM.

Cross-sectional survey of biosimilar insulin utilization in Asia: The Joint Asia Diabetes Evaluation Program.

AIMS/INTRODUCTION: Biosimilar insulin can reduce treatment costs, although the extent of its use is largely unknown. We examined biosimilar insulin use and its associations with the quality of glycemic control using the Joint Asia Diabetes Evaluation register. MATERIALS AND METHODS: We carried out a cross-sectional analysis in 81,531 patients with type 1 and type 2 diabetes enrolled into the Joint Asia Diabetes Evaluation Program from 2007 to 2014. All insulin related terms are extracted from the Joint Asia Diabetes Evaluation portal, and compared clinical profiles between biosimilar and originator insulin users. Multivariate analysis was performed to assess the association of biosimilar insulin compared with originator insulin with dosage, glycated hemoglobin and hypoglycemia events. RESULTS: Amongst 81,531 patients, 20.5% (n = 16,738) were insulin-treated. In four countries with high use of biosimilar insulin, 4.7% (n = 719) of insulin users (n = 10,197) were treated with biosimilar insulin (India n = 507, 70.3%; the Philippines n = 90, 12.5%; China n = 62, 8.6%; Vietnam n = 60, 8.3%). Biosimilar insulin users were younger and had higher body mass index, glycated hemoglobin, insulin dosage and more frequent hypoglycemia than originator insulin users. These associations were non-significant after adjustment for confounders. Only age, college education, diabetes education, lipid control, physical activity and history of cardiovascular complications were independently associated with these quality measures. CONCLUSIONS: Biosimilar insulin use is not uncommon in Asia. Data exclusion due to incomplete capturing of brand names suggests possibly higher use. The multiple determinants of the quality of glycemic control call for establishment of prospective cohorts and diabetes registers to monitor the safety and efficacy of different brands of biosimilar insulin and their impacts on clinical outcomes.

Evidence-based recommendations for insulin intensification strategies after basal insulin in type 2 diabetes.

Over the time due to progressive nature of diabetes, proactive intensification of the existing insulin therapy becomes imminent as it minimizes patients' exposure to chronic hypo/hyperglycaemia and reduces weight gain while achieving individualized glycaemic targets. This review focuses on the strength of evidence behind various options for intensification, primarily the insulins as also the GLP-1 analogues. The recommendations presented here are meant to serve as a guide for the physician managing type 2 diabetes patients requiring insulin intensification upon failing of basal insulin therapy.

Improved Medication Adherence and Frequency of Blood Glucose Self-Testing Using an m-Health Platform Versus Usual Care in a Multisite Randomized Clinical Trial Among People with Type 2 Diabetes in India.

BACKGROUND: In 2015, India had an estimated 69.2 million people with diabetes and a national prevalence of 8.7%. Evidence is mounting for the benefits of telemedicine in diabetes care, but remains limited on mobile-health (m-Health) interventions. INTRODUCTION: This study assessed the impact of an m-Health diabetes platform on clinical outcomes, patient-reported outcomes, patient and provider satisfaction, and app usage. MATERIALS AND METHODS: This open-label, two-arm parallel study enrolled 91 people at 3 sites in India, aged 18-65, with type 2 diabetes, and an A1c between 7.5% and 12.5% (58-113 mmol/mol). Participants were randomly assigned 1:1 to m-Health or usual care and observed for 6 months. All received free visits, laboratory tests, transportation fees, and strips and lancets. Intervention participants received the m-Health app and a mobile phone data stipend. RESULTS: A1c change was previously reported as statistically significant. Significantly more participants in intervention than control had improved medication adherence (39.0% vs. 12.8%; p = 0.03) and increased frequency of blood glucose (BG) self-testing (39.0% vs. 10.3%; p = 0.01) at 6 months from baseline. No other outcomes were significantly different. Among m-Health users, 75% of participants actively used the app at week 24. Participants entered 29,668 medications and 2,575 BG readings, sent 497 messages, and received 890 messages. Most participants (80%) were satisfied with all aspects of the app and all seven providers rated the software very acceptable. DISCUSSION: Participants assigned to m-Health had increased medication adherence and frequency of BG testing compared with usual care participants. CONCLUSIONS: This tool could be an effective way to expand access to quality chronic disease care and improve outcomes.

Retrospective Comparison of Clinical Characteristics and In-Hospital Outcomes among Diabetic and Non-Diabetic Adults with Acute Pyelonephritis.

INTRODUCTION: Acute Pyelonephritis (APN) is a common infection in community. Diabetes Mellitus (DM) may have different effect on clinical characteristics and outcomes of APN compared to non-diabetic individuals. AIM: To compare clinical characteristics and assess outcomes of APN patients with and without DM. MATERIALS AND METHODS: A retrospective analysis of 122 patients with DM (n=61) and without DM (n=61) was conducted at a single, private, urban set-up from Gujarat, India. Clinical symptoms, laboratory investigations, antibiotics treatment and outcomes in terms of mortality and prolonged hospitalization (10 days and above) were compared in two groups. RESULTS: Mean age was significantly higher in diabetics than non-diabetics (55.2±12.5 vs 41.5±17.3, p<0.0001) and females were proportionally higher in both groups (65.6% Vs 62.3%, p=0.706). Fever was most frequent symptom (83.6% Vs 90.2%, p=0.283) followed by nausea/vomiting (50.8% Vs 63.9%, p=0.143), dysuria (66.7% Vs 74.4%, p=0.433) and flank pain (8.2 Vs 13.1, p=0.379). Backache/back pain (47.5% Vs 29.5%, p=0.041) and Chronic Kidney Disease (CKD) (63.9% Vs 45.9%, p=0.045) were significantly higher in diabetics than non-diabetics. Mean hospital stay did not vary significantly in two groups (7.0±3.2 Vs 6.50±2.9, p=0.346) but proportion of patients with longer hospital stay was higher in DM (16.4% Vs 8.2%). Elevated white cell count, erythrocyte sedimentation rate, C-reactive protein, serum creatinine and presence of red cell in urine (> 5/ high power field [hpf]) did not vary significantly in two groups. Cephalosporin-beta-lactamase inhibitor (Cefaperazone-Sulbactam/Cefepime-Tazobactam) was the most prescribed antibiotic in both the groups. No deaths were observed in any group during this evaluation period. Only raised ESR (>30 mm/hr) {Odds Ratio (OR): 1.58, 95% Confidence Interval (CI) 1.36-1.82, p=0.004} and presence of CKD (OR: 1.71, 95% CI 1.30-2.25, p=0.008) were found to be the significant predictors of prolonged hospitalization in overall population. CONCLUSION: APN in diabetic and non-diabetic patients has similar clinical characteristics. Impact of diabetes on clinical outcomes of mortality and prolonged hospitalization warrants further investigation in a large, randomized, prospective trial.