Evaluating Glycemic Control Efficacy and Safety of the Oral Small Molecule Glucagon-Like Peptide 1 Receptor Agonist Danuglipron in Type 2 Diabetes Patients: A Systemic Review and Meta-Analysis.

Introduction: Diabetes Mellitus (DM) is a significant global health concern, with Type 2 DM (T2DM) being highly prevalent. Glucagon-Like Peptide 1 receptor agonists (GLP-1RA), such as Danuglipron, offer potential benefits in T2DM management. This meta-analysis examines the safety and efficacy of Danuglipron, focusing on adverse outcomes and glycemic parameters. Methods: A systematic search was conducted in PubMed, Scopus, and Cochrane Library for RCTs involving Danuglipron till August 2023, following PRISMA guidelines. The Cochrane risk-of-bias tool was used for quality assessment. Adverse outcomes (diarrhea, nausea, vomiting, headache, decreased appetite, dyspepsia, dizziness) and glycemic parameters like changes in HbA1C, fasting plasma glucose (FPG), and body weight were analyzed. Results: Four RCTs published from 2021 to 2023 were included. Both doses of Danuglipron were associated with diarrhea (RR=2.66, 90% CI: 1.32 to 5.35, p=0.02), nausea (RR=5.5, 90% CI: 3.4 to 8.88, p<0.00001), and vomiting (RR=5.98, 90% CI: 2.93 to 12.23, p=0.0001). The 120mg dose showed decreased appetite (RR=3.46, 90% CI: 1.57 to 7.62, p=0.01), dyspepsia (RR=4.04, 90% CI: 1.93 to 8.43, p=0.002), and dizziness (RR=5.08, 90% CI: 1.45 to 17.82, p=0.03). Reductions in HbA1C (SMD -1.09, 90% CI -1.39 to -0.8, p < 0.00001), FPG (SMD -1.10, 90% CI -1.46 to -0.75, p < 0.00001), and body weight (SMD -1.08, 90% CI -1.42 to -0.74, p < 0.00001) were observed for both doses. Conclusion: Danuglipron demonstrates potential for glycemic control and weight reduction in T2DM. Adverse outcomes include diarrhea, nausea, vomiting, and decreased appetite, with dose-related effects. Clinicians must weigh benefits against side effects when considering Danuglipron for T2DM management.

Advances in Polatuzumab Vedotin-PIIQ Therapy: A Review of Treatment Efficacy in Diffuse Large B Cell Lymphoma and High-Grade B Cell Lymphoma.

Polatuzumab vedotin (PV) is an antibody-drug conjugate that has shown promising results in the treatment of diffuse B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBCL). This abstract summarizes the current understanding of PV's use in these malignancies based on available clinical data. Multiple clinical trials have evaluated PV as a part of combination therapy regimens in relapsed/refractory DLBCL and HGBCL. The pivotal Phase II study, GO29365, demonstrated that PV in combination with bendamustine and rituximab (BR) significantly improved progression-free survival and overall survival compared to BR alone in patients with relapsed/refractory DLBCL who ineligible for stem cell transplantation were. Subsequently, the US Food and Drug Administration granted accelerated approval to PV in this setting. PV's mechanism of action involves targeting CD79b, a cell surface receptor expressed in B-cell malignancies, and delivering the cytotoxic agent monomethyl auristatin E to CD79b-expressing cells. This approach enhances the selective killing of cancer cells while sparing normal cells. The safety profile of PV is generally manageable, with adverse events including infusion-related reactions, cytopenia, peripheral neuropathy, and infections. Overall, PV has emerged as a valuable treatment option for patients with relapsed/refractory DLBCL and HGBCL, offering improved outcomes when combined with appropriate chemotherapy regimens. Ongoing research and clinical trials are further exploring PV's potential in various treatment settings, including frontline therapy and in combination with other novel agents.

Sodium stibogluconate (SSG) & paromomycin combination compared to SSG for visceral leishmaniasis in East Africa: a randomised controlled trial.

BACKGROUND: Alternative treatments for visceral leishmaniasis (VL) are required in East Africa. Paromomycin sulphate (PM) has been shown to be efficacious for VL treatment in India. METHODS: A multi-centre randomized-controlled trial (RCT) to compare efficacy and safety of PM (20 mg/kg/day for 21 days) and PM plus sodium stibogluconate (SSG) combination (PM, 15 mg/kg/day and SSG, 20 mg/kg/day for 17 days) with SSG (20 mg/kg/day for 30 days) for treatment of VL in East Africa. Patients aged 4-60 years with parasitologically confirmed VL were enrolled, excluding patients with contraindications. Primary and secondary efficacy outcomes were parasite clearance at 6-months follow-up and end of treatment, respectively. Safety was assessed mainly using adverse event (AE) data. FINDINGS: The PM versus SSG comparison enrolled 205 patients per arm with primary efficacy data available for 198 and 200 patients respectively. The SSG & PM versus SSG comparison enrolled 381 and 386 patients per arm respectively, with primary efficacy data available for 359 patients per arm. In Intention-to-Treat complete-case analyses, the efficacy of PM was significantly lower than SSG (84.3% versus 94.1%, difference = 9.7%, 95% confidence interval, CI: 3.6 to 15.7%, p = 0.002). The efficacy of SSG & PM was comparable to SSG (91.4% versus 93.9%, difference = 2.5%, 95% CI: -1.3 to 6.3%, p = 0.198). End of treatment efficacy results were very similar. There were no apparent differences in the safety profile of the three treatment regimens. CONCLUSION: The 17 day SSG & PM combination treatment had a good safety profile and was similar in efficacy to the standard 30 day SSG treatment, suggesting suitability for VL treatment in East Africa. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.govNCT00255567.

Geographical variation in the response of visceral leishmaniasis to paromomycin in East Africa: a multicentre, open-label, randomized trial.

BACKGROUND: Visceral leishmaniasis (VL) is a major health problem in developing countries. The untreated disease is fatal, available treatment is expensive and often toxic, and drug resistance is increasing. Improved treatment options are needed. Paromomycin was shown to be an efficacious first-line treatment with low toxicity in India. METHODS: This was a 3-arm multicentre, open-label, randomized, controlled clinical trial to compare three treatment regimens for VL in East Africa: paromomycin sulphate (PM) at 15 mg/kg/day for 21 days versus sodium stibogluconate (SSG) at 20 mg/kg/day for 30 days; and the combination of both dose regimens for 17 days. The primary efficacy endpoint was cure based on parasite-free tissue aspirates taken 6 months after treatment. FINDINGS: Overall, 135 patients per arm were enrolled at five centres in Sudan (2 sites), Kenya (1) and Ethiopia (2), when the PM arm had to be discontinued due to poor efficacy. The trial has continued with the higher dose of PM as well as the combination of PM and SSG arms. These results will be reported later. Baseline patient characteristics were similar among treatment arms. The overall cure with PM was significantly inferior to that with SSG (63.8% versus 92.2%; difference 28.5%, 95%CI 18.8% to 38.8%, p<0.001). The efficacy of PM varied among centres and was significantly lower in Sudan (14.3% and 46.7%) than in Kenya (80.0%) and Ethiopia (75.0% and 96.6%). No major safety issues with PM were identified. CONCLUSION: The efficacy of PM at 15 mg/kg/day for 21 days was inadequate, particularly in Sudan. The efficacy of higher doses and the combination treatment warrant further studies.

Paromomycin for the treatment of visceral leishmaniasis in Sudan: a randomized, open-label, dose-finding study.

BACKGROUND: A recent study has shown that treatment of visceral leishmaniasis (VL) with the standard dose of 15 mg/kg/day of paromomycin sulphate (PM) for 21 days was not efficacious in patients in Sudan. We therefore decided to test the efficacy of paramomycin for a longer treatment duration (15 mg/kg/day for 28 days) and at the higher dose of 20 mg/kg/day for 21 days. METHODS: This randomized, open-label, dose-finding, phase II study assessed the two above high-dose PM treatment regimens. Patients with clinical features and positive bone-marrow aspirates for VL were enrolled. All patients received their assigned courses of PM intramuscularly and adverse events were monitored. Parasite clearance in bone-marrow aspirates was tested by microscopy at end of treatment (EOT, primary efficacy endpoint), 3 months (in patients who were not clinically well) and 6 months after EOT (secondary efficacy endpoint). Pharmacokinetic data were obtained from a subset of patients weighing over 30 kg. FINDINGS: 42 patients (21 per group) aged between 4 and 60 years were enrolled. At EOT, 85% of patients (95% confidence interval [CI]: 63.7% to 97.0%) in the 20 mg/kg/day group and 90% of patients (95% CI: 69.6% to 98.8%) in the 15 mg/kg/day group had parasite clearance. Six months after treatment, efficacy was 80.0% (95% CI: 56.3% to 94.3%) and 81.0% (95% CI: 58.1% to 94.6%) in the 20 mg/kg/day and 15 mg/kg/day groups, respectively. There were no serious adverse events. Pharmacokinetic profiles suggested a difference between the two doses, although numbers of patients recruited were too few to make it significant (n = 3 and n = 6 in the 20 mg/kg/day and 15 mg/kg/day groups, respectively). CONCLUSION: Data suggest that both high dose regimens were more efficacious than the standard 15 mg/kg/day PM for 21 days and could be further evaluated in phase III studies in East Africa.

Unusual presentation of amoebic liver abscess.

Two cases of amoebic liver abscess are described. The unusual, purely left pleuritic, presentation in the first patient is emphasised. Amoebic liver abscess should still be thought of in any patient presenting with an acute febrile illness, upper abdominal and or thoracic manifestations and polymorphonuclear leucocytosis. Such a consideration should obviate unnecessary morbidity, mortality and the injudicious use of ineffective therapeutic agents.