Evaluating the Efficacy, Safety, and Tolerability of Combination Therapy of Dapagliflozin and Linagliptin Over Dapagliflozin and Vildagliptin in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin.

Background Type 2 diabetes mellitus (T2DM) patients commonly undergo metformin monotherapy. This study aims to compare the efficacy, safety, and tolerability of combination therapy of dapagliflozin plus linagliptin versus dapagliflozin plus vildagliptin as add-on therapy in T2DM patients inadequately controlled on metformin. Methodology This was an 18-week, multicenter, randomized, double-blind, active-controlled, parallel-group, phase III clinical study. About 236 participants were randomly assigned to receive either a fixed-dose combination of dapagliflozin 10 mg plus linagliptin 5 mg tablets or a fixed-dose combination of dapagliflozin 10 mg plus vildagliptin SR 100 mg tablets added to metformin monotherapy. The primary outcome was the mean change in hemoglobin A1c (HbA1c) from baseline to the end of week 16. The key secondary endpoints were mean change in postprandial blood glucose (PPBG), fasting blood glucose (FBG), body weight, and the proportion of participants achieving HbA1c less than 7.0%. Results The dapagliflozin/linagliptin combination therapy showed a more significant change in HbA1c from baseline to the end of 16 weeks (mean reduction: -1.59% vs. -1.25%) compared to dapagliflozin/vildagliptin (p < 0.0001). Additionally, compared to the dapagliflozin/vildagliptin group, the dapagliflozin/linagliptin group demonstrated a significant reduction in both PPBG (mean reduction: -59.99 mg/dL vs. -55.34 mg/dL) and FPG (mean reduction: -32.91 mg/dL vs. -26.78 mg/dL). A total of 18 adverse events were reported in 17 (7.20%) participants, all of which were mild and resolved completely. There were no serious adverse events. Conclusions Compared to dapagliflozin and vildagliptin combination therapy, dapagliflozin and linagliptin fixed-dose combination provided clinically significant improvements in glycemic control. Because of its effectiveness, safety, and tolerability, the fixed-dose combination of dapagliflozin and linagliptin was a better option for treating T2DM patients who had previously only received metformin monotherapy.

Efficacy and safety of pegylated interferon-α2b in moderate COVID-19: a phase 3, randomized, comparator-controlled, open-label study.

OBJECTIVE: To evaluate the efficacy and safety of pegylated interferon alpha-2b (PEG IFN-α2b) administered in conjunction with the standard of care (SOC) in subjects with moderate coronavirus disease-19 (COVID-19). METHODS: In this study, adult subjects with confirmed moderate COVID-19 were randomized in a 1:1 ratio to receive either PEG IFN-α2b + SOC or SOC alone. The primary endpoint was a two-point improvement in clinical status on Day 11, measured by the World Health Organization's seven-point ordinal scale. RESULTS: Of 250 subjects, 120 were randomized to the PEG IFN-α2b + SOC arm and 130 were randomized to the SOC arm. The results for the PEG IFN + SOC arms vs the SOC arm for the proportion of subjects with a two-point improvement in the seven-point ordinal scale were 80.36% vs 68.18% (P=0.037) on Day 8, 91.60% vs 92.56% (P=0.781) on Day 11, and 94.12% vs 95.93% (P=0.515) on Day 15. There was a time-dependent decrease in the biomarkers in both arms, and no clinically significant changes in laboratory parameters. The safety profile was similar in both arms. CONCLUSION: PEG IFN-α2b induced early viral clearance, improved the clinical status, and decreased the duration of supplemental oxygen. It provides a viable treatment option and can limit the spread of severe acute respiratory syndrome coronavirus-2.

Study of Vitamin B12 deficiency and peripheral neuropathy in metformin-treated early Type 2 diabetes mellitus.

BACKGROUND: Long-term therapy with metformin was shown to decrease the Vitamin B12 level and manifested as peripheral neuropathy. AIM: The aim of this study is to define the prevalence of Vitamin B12 deficiency in early Type 2 diabetic patients (duration ≤5 years or drug treatment ≤3 years) and the relationship among metformin exposure and levels of cobalamin (Cbl), folic acid, and homocysteine (Hcy) with severity of peripheral neuropathy. METHODOLOGY: This is a cross-sectional study involving randomly selected ninety patients (male 56, female 34) between age groups of 35 and 70 years, comparing those who had received >6 months of metformin (Group A) (n = 35) with those without metformin (Group B) (n = 35) and patients taking metformin with other oral hypoglycemic agent (Group C) (n = 20). Comparisons were made clinically, biochemically (serum Cbl, fasting Hcy, and folic acid), and with electrophysiological measures (nerve conduction studies of all four limbs). Comorbidities contributing to neuropathy were excluded from the study. RESULTS: Group A patients (54.28%) were prone to develop peripheral neuropathy comparing Group B (28.57%) and Group C (35%). There was significantly low plasma level of Cbl in Group A (mean 306.314 pg/ml) than in Group B (mean 627.543 pg/ml) and Group C (mean 419.920 pg/ml). There was insignificant low-level plasma folic acid in Group A (16.47 ng/ml) than in Group B (16.81 ng/ml) and Group C (22.50 ng/ml). There was significantly high level of Hcy in Group A (mean 17.35 µmol/L) and Group C (mean 16.99 µmol/L) than in Group B (mean 13.22 µmol/L). Metformin users even for 2 years showed evidence of neuropathy on nerve conduction velocity though their body mass index and postprandial blood sugar were maintained. There was significant difference in between groups regarding plasma Cbl, folic acid, and Hcy level as significance level <0.05 in all three groups (F [2, 87] = 28.1, P = 0.000), (F [2, 87] = 7.43, P = 0.001), (F [2, 87] = 9.76, P = 0.000). Post hoc study shows significant (P < 0.05) lowering of Cbl and Hcy level in Group A (mean = 306.314, standard deviation [SD] = 176.7) than in Group C (mean = 419.92, SD = 208.23) and Group B (mean = 627.543, SD = 168.33). DISCUSSION: Even short-term treatment with metformin causes a decrease in serum Cbl folic acid and increase in Hcy, which leads to peripheral neuropathy in Type 2 diabetes patients. A multicenter study with heterogeneous population would have increased the power of the study. We suggest prophylactic Vitamin B12 and folic acid supplementation or periodical assay in metformin user.

Correlation of intracranial atherosclerosis with carotid stenosis in ischemic stroke patients.

INTRODUCTION: Carotid stenosis is a major risk factor for ischemic stroke. However, the effect of carotid stenosis on the site of stroke is still under investigation. AIMS: This study aimed to elucidate how the presence of carotid stenosis influenced the pattern of stroke and also how it interacted with other risk factors for stroke. MATERIALS AND METHODS: Thirty-eight patients with ischemic stroke were included in this study and were investigated with carotid artery Doppler and magnetic resonance angiography for carotid stenosis and intracranial stenosis in the circle of Willis, respectively. Other known risk factors of stroke were also studied in and compared between the subgroups with and without carotid stenosis. RESULTS: In patients without carotid stenosis, anterior cerebral artery was the commonest site of stenosis. In patients with carotid stenosis, middle cerebral artery was the commonest site of stenosis. Overall, middle cerebral artery was the commonest territory of stroke. Patients with hypertension, diabetes and history of smoking had preferential stenosis of the anterior cerebral artery.

Prevalence of Skin Changes in Diabetes Mellitus and its Correlation with Internal Diseases: A Single Center Observational Study.

BACKGROUND AND AIM: This single-center observational cross-sectional study has been done in an attempt to find out the prevalence of various skin manifestations in diabetes patients (DM) and their correlation with diabetes control and complications. MATERIALS AND METHODS: Skin manifestations present over 12 months among those attend diabetes clinic were included in the study. Apart from demographic data and type, patients were also screened for micro vascular complications and control of diabetes over last 3 months. RESULTS AND DISCUSSION: Sixty (n = 60) diabetes patisents (Type 1 DM, 9 patients and Type 2 DM 51 patients) have been found to have various skin lesions. Thirty-one (51.67%) patients presented with infectious conditions, vascular complications were present in 21 (35%) and dermatomes belonging to the miscellaneous group were present in 50 (83.33%) patients. Pyoderma, diabetic dermopathy, and pruritus without skin lesions were found to be most common manifestations in infective, vascular and miscellaneous group, respectively. Higher level of HB1AC was found in patient with diabetic bulla (10.5 ± 0), scleredema (9.75 ± 0.77), lichen planus (9.3 ± 1.6), and acanthosis nigricans (9.15 ± 0.89). Patients with psoriasis and vitiligo had statistically significant lower level of glycosylated hemoglobin (P =< 0.001 and 0.03, respectively). However, no association of any kind of skin manifestation with DM with other microangiopathic complications was found in this study.

Spindle Cell Hemangioendothelioma: Rare Clinical Entity.

Spindle-cell hemangioendothelioma (SCHE) comprise a rare subset of vascular tumors, and here, we describe such a case and review the clinical presentation, patho-physiology, differential diagnosis of these tumors to promote early identification and discussion guidance. A 25-years-old male patient presented with multiple painful elevated swellings of both left upper and lower extremities for last 15 years without any systemic involvement. After excluding close differential diagnosis by relevant investigations an excisional biopsy was performed. Based on clinical, radiological and histopathological findings, diagnosis of SCHE was made and full thickness excision and skin grafting were performed. The case is reported due to its rarity and adds our knowledge to the existing literature.

Cerebellar ataxia in a young patient: A rare path to lupus.

Cerebellar ataxia is a rare manifestation of neuropsychiatric systemic lupus erythematosus (SLE). Development of vasculitic infarcts in the cerebellum is the most plausible reason of this manifestation. We report the case of a patient who presented with characteristic skin rashes of lupus along with cerebellar signs. Imaging of brain in this patient revealed prominent cerebellar atrophy. She was treated with mycophenolate mofetil and oral corticosteroid, and there was no further progression of her neurological signs after the initiation of therapy. In the clinical context of varied presentations of neurolupus, this is one of the rare sightings and our treatment protocol holds promise as first-line therapy in future.

A commonly overlooked motor neuron disease mimicker.

UNLABELLED: Motor neuron disease (MND) is a progressive devastating neurodegenerative disease, which universally progresses towards death. Hence, every attempt should be made to find out if there are any treatable conditions, which can mimic MND. Herein, we describe a case of hypercalcaemia due to primary hyperparathyroidism confused as MND and subsequently cured with parathyroid surgery. LEARNING POINTS: Any patient with neurological disorder should have a screening of all the common electrolytes including calcium as electrolyte imbalance can present with paralysis (e.g. hypokalaemia) to amyotrophic lateral sclerosis (e.g. hypercalcaemia).No patient should be stamped as having MND without having a proper work-up of all its differentials as there might be a treatable condition masquerading as MND.