Comparative clinical efficacy and safety of insulin glargine 300 U/ml (Toujeo) versus insulin glargine 100 U/ml in type 2 diabetes and type 1 diabetes: A systematic literature review and meta-analysis.

AIM: To compare the clinical efficacy and safety of glargine-U100 (Lantus/Gla-100) with glargine-U300 (Toujeo/Gla-300) in adult patients with type 2 diabetes (T2D) and type 1 diabetes (T1D). MATERIALS AND METHODS: A literature search on Gla-300/Gla-100 in diabetes management was conducted using the MEDLINE/Embase/Cochrane databases from inception to 10 January 2021. Eligible studies considered for inclusion were parallel-design, randomized controlled trials (RCTs). The Cochrane risk-of-bias tool was used to evaluate the quality of the included studies. The random-effects model was applied for interpretation of the results. RESULTS: Of 5348 records screened, 592 were assessed for eligibility and 15 RCTs were considered for data extraction and meta-analysis (T2D [N = 10; n = 7082]; T1D [N = 5; n = 2222]). In patients with T1D, all safety parameters were comparable between Gla-100 and Gla-300. In T2D, statistically significant differences were observed in favour of Gla-300 over Gla-100 for nocturnal and total hypoglycaemia. For efficacy parameters, a statistically and clinically significant difference favouring Gla-100 in basal insulin dose requirement was observed for both T2D and T1D. Change in HbA1c showed a statistically but not clinically significant reduction with Gla-100 compared with Gla-300 in T1D. Statistically significant but clinically less relevant differences favoured Gla-300 for control of body weight in T1D and T2D and Gla-100 for fasting blood glucose in T2D. CONCLUSIONS: Gla-100 and Gla-300 had comparable efficacy and safety profiles in both T1D and T2D populations. Gla-300 showed a lower risk of nocturnal and total hypoglycaemia, significant in insulin-experienced/exposed patients with T2D. Patients on Gla-300 required significantly more units of insulin daily than the Gla-100 group to achieve equivalent efficacy.

Biosimilars and interchangeable biosimilars: facts every prescriber, payor, and patient should know. Insulins perspective.

INTRODUCTION: For many of the 537 million adults living now with diabetes, the cost of insulin is becoming prohibitive as the insulin prices have tripled between 2002-2013. Globally, the direct annual cost of healthcare expenditure due to diabetes will soon be US$1 Trillion. Biosimilars provide access to high-quality, affordable biologic therapy that is otherwise inaccessible due to the high costs of original biologics. AREAS COVERED: A primer to the development of biosimilars shows comparable structural and analytical characterization to the original biologics (e.g. insulins), with no clinically significant or meaningful differences in efficacy and safety. 'Interchangeability' status, a regulatory designation by the US FDA, bestowed to some biosimilars, enables confidence in high-quality, bio-equivalent biosimilar of insulin with key global approvals. This can allow rapid uptake of biosimilars by the prescribers, formulary decision-makers, and payors. Biocon-Viatris's biosimilar Insulin Glargine (Semglee®) is the first interchangeable biosimilar insulin approved by the US FDA. EXPERT OPINION: The 'interchangeable' status can prompt faster and wider uptake of insulin biosimilars and keep the insulin expenditure under control, especially for patients who otherwise practice non-adherence or rationing of life-saving insulin. Education, support, and awareness can ensure that interchangeable biosimilars gain wider acceptance.

Expert Opinion on Usage of Pidotimod in Adult Patients with Chronic Obstructive Pulmonary Disease: An Indian Perspective.

India has a disproportionately high burden of acute and chronic pulmonary diseases. In India, 65 million suffer from non-communicable respiratory diseases. The outbreak of the novel coronavirus disease 2019 (COVID-19) had worsened the situation. Patients affected with COVID-19 with a previous history of comorbidities, such as COPD and chronic lung diseases, had the worst prognosis, resulting in adverse outcomes, such as acute respiratory distress syndrome (ARDS) and pneumonia. Immune modulation strategies have since gained a lot of traction amongst practitioners. Modulation of the immune system with Pidotimod along with standard-of-care (SOC) treatment has proven efficacious in the past two decades in patients with recurrent respiratory tract infections (RRTIs), bronchitis, COPD, and pneumonia. In this article, we have reviewed the current unmet needs in the management of COPD in India and evaluated the usage of Pidotimod in adult COPD patients based on expert panel discussion.

Sodium-glucose co-transporter-2 inhibitors: A cardiovascular outcome trial analysis.

Cardiovascular outcome trials (CVOTs) have to be done by sponsors who wish to launch new antidiabetic drugs in the US, since the December 2008 US Food and Drug Administration ruling, which was subsequently accepted by the European Medicines (Evaluation) Agency (EMA) in 2012. However, the medical community asks the question, "So What?" as they are not convinced of the clinical relevance of CVOTs. The patients selected in CVOTs are necessarily high risk, so that they develop major adverse cardiovascular events quickly, but then, the results are extrapolatable to only a certain percentage of patients seen in the clinical practice. Doctors believe that these trials only serve a regulatory need. At the same time, these trials do provide a lot of good data, but it needs to be interpreted well, and extrapolated appropriately to patients in practice as there are differences between what happens in a randomized control trial and in the real world. Hence, the need for this article which serves to dissect the CVOTs of sodium-glucose co-transporter-2 inhibitors, so that doctors are able to better read this evidence. However, the question of which gliflozin is the best cannot be answered by these trials as these are not head to head trials. All the more reason why one needs to look at the data holistically and be empowered to make the right decision for individual patients, hoping to match the best patient for the best drug, rather than determine which drug is better.

Blood pressure and heart rate related to sex in untreated subjects: the India ABPM study.

Women are underrepresented in groups of patients seeking hypertension care in India. The present paper reports trends in office and ambulatory blood pressure measurement (OBPM, ABPM) and 24-h heart rate (HR) with sex in 14,977 subjects untreated for hypertension (aged 47.3 ± 13.9 years, males 69.4%) visiting primary care physicians. Results showed that, for systolic blood pressure (SBP), females had lower daytime ABPM (131 ± 16 vs. 133 ± 14 mm Hg, P < .001) but higher nighttime ABPM (122 ± 18 vs. 121 ± 16 mm Hg, P < .001) than males. Females had higher HR than men at daytime (80 ± 11 vs 79 ± 11.5 bpm) and nighttime (71 ± 11 vs 69 ± 11), respectively (all P < .001). Dipping percentages for SBP (7.4 ± 7.3 vs 9.3 ± 7.4%), DBP (10.1 ± 8.6 vs. 12.3 ± 8.9%), and HR (10.7 ± 7.9 vs. 12.8 ± 9.2%) were lower (P < .001) for females than for males, respectively. Females more often had isolated nighttime hypertension as compared to males (14.9%, n = 684% vs 10.6%, n = 1105; P < .001). BP patterns and HR showed clear differences in sex, particularly at nighttime. As females were more often affected by non-dipping and elevated nighttime SBP and HR than males, they should receive ABPM, at least, as frequently as men to document higher risk necessitating treatment.

Self-blood pressure measurement as compared to office blood pressure measurement in a large Indian population; the India Heart Study.

OBJECTIVE: India Heart Study (IHS) is aimed at investigating the agreement between office blood pressure measurement (OBPM) and self (S)BPM in a hypertension-naive population. METHODS: A total of 18 918 individuals (aged 42.6 ±â€Š11.7 years, 62.7% men), visiting 1237 primary care physicians across India, underwent OBPM. They performed SBPM for a period of 1 week using a validated oscillometric BP monitor that was preprogrammed to adhere to a guideline-based SBPM-schedule and blinded to the results. Thereafter, individuals underwent a second OBPM. Available laboratory results were obtained. Thresholds for elevated OBPM and SBPM were 140/90 and 135/85 mmHg, respectively. RESULTS: On the basis of first-visit OBPM and SBPM, there were 5787 (30.6%) individuals with normotension; 5208 (27.5%) with hypertension; 4485 (23.7%) with white-coat hypertension (WCH) and 3438 (18.2%) with masked hypertension. Thus, a diagnosis contradiction between SBPM and first-visit OBPM was seen in 9870 (41.9%) individuals. On the basis of second-visit OBPM, the normotension, hypertension, WCH and masked hypertension prevalence values were 7875 (41.6%); 4857 (25.7%); 2397 (12.7%) and 3789 (20.0%). There was poor agreement (kappa value 0.37) between OBPM of visit 1 and 2 with a diagnosis difference in 6027 (31.8%) individuals. The majority of masked hypertension and WCH individuals had BP values close to thresholds. CONCLUSION: There was a poor agreement between OBPM of visit1 and visit 2. Likewise, the agreement between OBPM at both visits and SBPM was poor. SBPM being considered to have a better correlation with patient prognosis should be the preferred method for diagnosing hypertension.

Usefulness of ambulatory blood pressure measurement for hypertension management in India: the India ABPM study.

The present paper reports differences between office blood pressure (BP) measurement (OBPM) and ambulatory blood pressure measurement (ABPM) in a large multi-centre Indian all comers' population visiting primary care physicians. ABPM and OBPM data from 27,472 subjects (aged 51 ± 14 years, males 68.2%, treated 45.5%) were analysed and compared. Patients were classified based on the following hypertension thresholds: systolic BP (SBP) ≥ 140 and/or diastolic BP (DBP) ≥90 mmHg for OBPM, and SBP ≥ 130 and/or DBP ≥ 80 mmHg for 24-h ABPM, and SBP ≥ 120 and/or DBP ≥ 70 mmHg for night-time ABPM and SBP ≥ 135 and/or DBP ≥ 85 mmHg for daytime ABPM, all together. White coat hypertension (WCH) was seen in 12.0% (n = 3304), masked hypertension (MH) in 19.3% (n = 5293) and 55.5% (n = 15,246) had sustained hypertension. Isolated night-time hypertension (INH) was diagnosed in 11.9% (n = 3256). Untreated subjects had MH relatively more often than treated subjects (23.0% vs. 14.8%, p < 0.0001; respectively). Females had higher relative risk (RR) of having WCH than males (RR 1.16 [CI 95, 1.07-1.25], p < 0.0001). Whereas, males had higher RR of MH than females (RR 1.09 [CI 95, 1.02-1.17] p < 0.01). INH subjects had lower average systolic and diastolic dipping percentages (0.7 ± 6.6/ 2.2 ± 7.9 vs. 9.0 ± 7.3/11.9 ± 8.5, p < 0.001) than those without INH. In conclusion, for diagnosis of hypertension there was a contradiction between OBPM and ABPM in approximately one-third of all patients, and a substantial number of patients had INH. Using ABPM in routine hypertension management can lead to a reduction in burden and associated costs for Indian healthcare.

Blood pressure related to age: The India ABPM study.

The present paper reports trends in office blood pressure (BP) measurement (OBPM) and ambulatory blood pressure measurement (ABPM) with age in a large multi-center Indian all comers' population visiting primary care physicians. ABPM and OBPM data from 27 472 subjects (aged 51 ± 14 years, males 68.2%, treated 45.5%) were analyzed and compared. Individual differences between OBPM and ABPM patterns were compared for patients according to 10-year age categories. Results showed that systolic (S) BP values started to increase with age from the age of 40, BP variability (SD) increased from the age of 30 years. Diastolic (D) BP values started to decrease from the age of 50 years. Mean OBPM values were higher than daytime ABPM values (all P < .001) in all age-groups. The prevalence of white coat hypertension (WCH) and masked hypertension (MH) was based on OBPM and daytime, 24-hour, and nighttime average BPs together. WCH decreased with age from 15.1% and 12.4% in treated and untreated subjects at the youngest age to 7.2% and 6.9% in the oldest age, respectively. MH prevalence was higher for untreated than for treated subjects but remained similar for all age-groups (range of 18.6%-21.3%). The prevalence of reverse dippers increased with age from the youngest to oldest group with 7.3%-34.2% (P < .001 for trend). Dippers prevalence decreased from 42.5% to 17.9% from the youngest to oldest age-groups, respectively (P < .001 for trend). These findings confirm that BP patterns show clear differences in trends with age, particularly regarding nighttime BP.

Real world evidence (RWE) - Are we (RWE) ready?

Real world evidence is important as it complements data from randomised controlled trials (RCTs). Both have limitations in design, interpretation, and extrapolatability. It is imperative one designs real world studies in the right way, else it can be misleading. An RCT is always considered higher in the evidence ladder and when there is discordance between a real world study and an RCT, it is the latter which is always considered pristine because of the way it is conducted, e.g., randomization, prospective, double-blind, etc. A real world study can also be done prospectively, and propensity score matching can be used to construct comparable cohorts but may not be able to account for certain biases or confounding factors the way an RCT can do. Nevertheless, comparative effectiveness research in the real world is being resorted to, especially for efficiency studies or pharmacoeconomic analyses, and with the advent of machine learning, the electronic healthcare database mining can result in algorithms that help doctors identify clinical characteristics that correlate with optimal response of a patient to a drug/regimen, thus helping him/her select the right patient for the right drug.

Long-Term Efficacy and Safety of Empagliflozin Monotherapy in Drug-Naïve Patients with Type 2 Diabetes in Indian Subgroup: Results from a 76-week Extension Trial of Phase III, Double-Blind, Randomized Study.

BACKGROUND AND OBJECTIVES: Empagliflozin, a sodium glucose cotransporter-2 inhibitor, was recently evaluated in a randomized, controlled trial (RCT) in drug-naïve Type 2 diabetes mellitus (T2DM) patients managed on diet and exercise therapy. Efficacy and safety of empagliflozin in Indian subgroup of patients from a 76-week extension study of the initial multicentric RCT are reported in this article. MATERIALS AND METHODS: In this study, patients were randomized to empagliflozin 10 mg (E10, n = 24), empagliflozin 25 mg (E25, n = 29), placebo (n = 28) and sitagliptin 100 mg (S100, n = 27). Exploratory efficacy endpoints were changed from baseline to week 76 in glycosylated hemoglobin (HbA1c, %) and fasting blood glucose (mg/dL) along with body weight (kg) and blood pressure (BP) (mmHg) reduction. Safety analysis included clinically relevant adverse events (AEs). RESULTS: In 108 randomized patients, adjusted mean reduction in HbA1c compared to placebo was significant with E10 (-0.81, 95% confidence interval (CI) -1.33, -0.28; P = 0.0029) and E25 (-1.11, 95% CI - 1.60, -0.61; P < 0.0001). HbA1c below 7% at week 76 was achieved in significantly higher number of patients with E10 (20.8%, P < 0.0001) and E25 (28.0%, P < 0.0001). There was significant reduction in adjusted mean weight as compared to placebo with E10 (-1.41, 95% CI - 2.51, -0.31; P = 0.0125) and E25 (-1.50, 95% CI - 2.54, -0.46; P = 0.0051) but nonsignificant with S100 (-0.75 95% CI - 1.86, -0.36; P = 0.1842). BP reduction was numerically higher with empagliflozin compared to placebo. AEs were similar in all treatment groups except for genital infections which were more common in E10 (20.8%) but not in E25 (3.4%) as compared to placebo (3.6%). All treatments were well tolerated with no severe AEs. CONCLUSION: Treatment with empagliflozin was well tolerated and resulted in sustained glycemic efficacy over long-term (76 weeks) in drug-naïve Indian T2DM patients.

Involvement of general public in biomedical research.

Biomedical research is crucial for any country's progress and the health of its ethnic population. This effort needs to be sustained and well supported for it to bear optimum results. The major stakeholders in medical research are the general public, patients, researchers, physicians (and medical institutions), the pharmaceutical industry, regulatory authorities, and the government. Much of the pressure to perform cutting edge research in developed countries is driven by the general public; however, this has been conspicuous by its absence in India. This is largely due to misconceptions that medical research in developing countries is an experimental exercise using human beings as guinea pigs, primarily benefiting only the pharmaceutical industry and a general lack of awareness about the importance of original research within the country. This editorial addresses various issues related to public involvement in biomedical research and suggests the need for solutions and imperative remedial measures.

Stroke Prevention in Atrial Fibrillation - Which is the BEST?: Balanced in Efficacy and Safety as a Thromboprophylactic.

Stroke prevention in atrial fibrillation (AF) has reached an exciting phase with a plethora of newer, potentially more efficacious and safer agents being introduced for physicians to select from. Dabigatran belongs to a class of anticoagulants called direct thrombin inhibitors, while rivaroxaban, apixaban, and edoxaban are direct Factor Xa inhibitors. Purely from a therapeutic endpoint perspective-based on the action of anticoagulants in reducing cardioembolic stroke-in clinical trials, one should look at whether a new anticoagulant in patients with AF prevents ischemic stroke. From a net clinical benefit perspective, one evaluates both efficacy and safety, which is when one includes association of stroke prevention with: hemorrhagic stroke; major, intracranial, life-threatening or total bleeding, etc. Interestingly, so far only dabigatran 150mg bid has been shown to be superior to well controlled warfarin in reducing the risk of ischemic stroke in patients with AF. Apixaban 5 mg bid, dabigatran 110 mg bid and both doses of edoxaban were superior to well controlled warfarin in being associated with a lower incidence of major bleeding. Apixaban 5 mg bid and edoxaban 30 mg od were superior to well controlled warfarin in reducing all-cause mortality. Clinicians will need to judiciously prescribe the right drug for the right patient, keeping many factors in consideration, and individualize the therapy based on underlying comorbidities and response to therapy.

Practical challenges in conducting respiratory studies.

Respiratory studies are complex on account of specific therapeutic knowledge that is needed and various instruments that are used for the management of this condition. Monitoring a respiratory study requires knowledge of the specific disease and associated guidelines. The intent of this article is to help clinical research professionals understand the technicalities, challenges, and the nuances of performing respiratory studies.

Treatment Costs of Stroke Related to Nonvalvular Atrial Fibrillation Patients in India-A Multicenter Observational Study.

OBJECTIVE: The objective of this study was to quantify the direct medical and nonmedical costs of stroke among patients with nonvalvular atrial fibrillation in India. METHODS: An observational, multicenter cost-of-illness study was conducted within large tertiary care hospitals across three metropolitan cities in India. Medical chart records of eligible patients who were hospitalized during the study period were reviewed. A standardized data collection form was designed and used to capture resources expended in the treatment and management of stroke during the inpatient stay. In addition, direct medical and nonmedical outpatient care resources and informal care burden were captured using a detailed questionnaire, following the patients' discharge. Factors associated with acute care costs were investigated using multivariate linear regression analysis. RESULTS: Data were collected on a total of 400 patients with incident strokes. Their mean age was 61.4 ± 9.4 years. About 84% of the patients were diagnosed with ischemic stroke. On average, patients spent 16 ± 10 days in the hospital. Total mean direct health care costs per patient amounted to `504,973 (US $8,020) during the first year, with about 47% (mean `235,471; US $3,750) of the total costs due to the index hospitalization. The modified Rankin scale score was strongly associated with costs, whereby severely disabled patients had 32% higher costs (P = 0.001) compared with moderately disabled patients during the first 3 months postdischarge. CONCLUSIONS: Overall, the financial burden associated with medical care for patients with stroke with atrial fibrillation along with rehabilitation and long-term care costs places a significant demand on health services in India.