Both dapagliflozin and glimepiride have their own set of benefits and considerations as adjunct medications to metformin in the management of Type 2 Diabetes Mellitus (T2DM). The choice between these two medications will depend on various factors including patient-specific needs, comorbidities, and preferences. Here's a comparison: Two medications, bexagliflozin and glimepiride, offer distinct advantages as adjuncts to metformin in managing Type 2 Diabetes Mellitus (T2DM). Bexagliflozin, an SGLT2 inhibitor, facilitates weight loss, reduces blood pressure, and carries a lower risk of hypoglycemia compared to glimepiride, which belongs to the sulfonylurea class and acts by stimulating insulin release. However, bexagliflozin may result in side effects like urinary tract infections and genital mycotic infections, whereas glimepiride poses a higher hypoglycemia risk and potential weight gain. The choice between these medications hinges on patient-specific factors. For individuals prioritizing weight loss or with concerns about hypoglycemia, bexagliflozin might be more suitable. Conversely,glimepiride could be considered for those needing rapid glucose reduction at a lower cost, despite its higher hypoglycemia risk and potential for weight gain. Assessing patient comorbidities and preferences becomes pivotal in selecting the most appropriate medication.

Bexagliflozin demonstrates comparable antidiabetic potency to glimepiride while offering additional benefits such as weight loss, blood pressure reduction, and potential renal and cardiovascular advantages. This reinforces the growing evidence favoring SGLT2 inhibitors, like bexagliflozin, as preferred options for long-term T2DM management, outperforming certain other oral hypoglycemic agents. However, personalized treatment decisions, based on individual patient needs and considerations, remain essential for optimizing diabetes management.

[1] Halvorsen, Y.-D., Lock, J. P., Frias, J. P., Tinahones, F. J., Dahl, D., Conery, A. L., & Freeman, M. W. (2023). A 96-week, double-blind, randomized controlled trial comparing bexagliflozin to glimepiride as an adjunct to metformin for the treatment of type 2 diabetes in adults. Diabetes, Obesity & Metabolism, 25(1), 293–301. https://doi.org/10.1111/dom.14875

[2] Maccari, R., & Ottanà, R. (2022). Sodium-Glucose Cotransporter Inhibitors as Antidiabetic Drugs: Current Development and Future Perspectives. Journal of Medicinal Chemistry, 65(16), 10848–10881. https://doi.org/10.1021/acs.jmedchem.2c00867

In a 96-week randomized study (N=426), patients taking metformin with adjunct medication of bexagliflozin 20 mg or titrated glimepiride 2-6mg were monitored. Bexagliflozin provided larger reductions in HbA1C, weight loss, and less hypoglycemia compared with glimepiride. At week 96, the intergroup differences for HbA1C were -0.21% and bexagliflozin was superior to glimepiride. Since glimepiride’s mechanism of action is by facilitation of insulin secretion, one major side effect is hypoglycemia, and it was very evident in this trial. In this trial, the proportion of subjects experiencing severe or documented symptomatic hypoglycemia was 3.3% in the bexagliflozin group and 20.8% in the glimepiride group. The p value was less than 0.0002 making it statistically significant. Bexagliflozin was also superior to glimepiride for reduction in body mass in subjects who were overweight or obese at baseline and for reduction in systolic blood pressure in subjects who were hypertensive at baseline. Lastly, bexagliflozin was superior at lowering fasting blood glucose and decreasing rate of decline of renal function. 

Although bexagliflozin HbA1C reduction compared to glimepiride  was not statistically significant, it was still lower and clearly has more benefits. Hypertension and chronic kidney disease are common comorbidities to diabetes and bexagliflozin has better renal and cardiovascular protection and thus is more favorable than glimepiride.

[1] Halvorsen, Y. D., Lock, J. P., Frias, J. P., Tinahones, F. J., Dahl, D., Conery, A. L., & Freeman, M. W. (2023). A 96-week, double-blind, randomized controlled trial comparing bexagliflozin to glimepiride as an adjunct to metformin for the treatment of type 2 diabetes in adults. Diabetes, obesity & metabolism, 25(1), 293–301. https://doi.org/10.1111/dom.14875

Respiratory synctial virus (RSV) is a common cause of acute lower respiratory tract infection in infants among varying demographics. Nirsevimab (Beyfortus) is a monoclonal antibody formulated as an intramuscular injection. It is used to prevent contraction of RSV by binding the RSV fusion protein and blocking entry into the host cell. 

In this study, infants of at least 35 weeks were randomly assigned to receive a single intramuscular injection of nirsevimab or placebo before the start of an RSV season. A total of 1490 infants participated in this study. 994 were assigned to the nirsevimab group, and 496 were assigned to the placebo group. Compared to the placebo group, the nirsevimab group experienced significantly less RSV-associated lower respiratory tract infection. Infection occurred in 12 infants (1.2%) in the nirsevimab group and in 25 infants (5.0%) in the placebo group. These findings correspond to an efficacy of 74.5%. According to this study, a single dose of the monoclonal antibody nirsevimab provided protection against RSV-associated lower respiratory tract infection when given to healthy infants before an RSV season.  

The safety profile of nirsevimab among recipients who were positive for antidrug antibodies after baseline was similar to that among recipients without antidrug antibodies. Serious adverse events were reported in 6.8% of nirsevimab recipients and in 7.3% of placebo recipients. However, none of these adverse events were considered to be related to nirsevimab or placebo. In one case, a nirsevimab recipient had a grade 3 generalized macular rash 6 days after the injection, which resolved without treatment. This event was considered to be related to nirsevimab. There were no other hypersensitivity reactions reported." 

[1] Hammitt LL et al., Nirsevimab for prevention of RSV in healthy late-preterm and term infants. The New England journal of medicine. Accessed November 26, 2023. https://pubmed.ncbi.nlm.nih.gov/35235726/.  

Given the newly diagnosis of FLT3-ITD-positive acute myeloid leukemia the use of quizartinib is appropriate. Quizartinib is a highly potent selective type 2 FLT3 inhibitor. However, it has only been researched in patients between the ages of 18 to 75 years old. So, to determine if the patient is a good candidate for this drug the patient would have to fall into this age group. The combination of quizartinib and cytarabine (an antimetabolite) a type of chemotherapeutic has shown to have promising effects on patients with this condition. Cytarabine can be administered as 100 mg/m 2 per day or up to 200 mg/m 2 per day max by continuous infusion on days 1 to 7. Daunorubicin 60 mg/m 2 per day or idarubicin 12 mg/m 2 per day can be administered on days 1, 2, and 3. Quizartinib 40 mg can then be started orally on day 8 for 14 days. The combination of the two drugs has shown to be effective than traditional monotherapy even as a consolidation therapy, with or without allo-HCT and the use of monotherapy as a continuation for up to 3 years has shown overall improvement in survival. The use of quizartinib is overall well tolerated in adult patients with the most common grade 3 or 4 adverse events being: neutropenia, hypokalemia, and pneumonia.

[1] Erba, H. P., Montesinos, P., Kim, H. J., Patkowska, E., Vrhovac, R., Žák, P., Wang, P. N., Mitov, T., Hanyok, J., Kamel, Y. M., Rohrbach, J. E. C., Liu, L., Benzohra, A., Lesegretain, A., Cortes, J., Perl, A. E., Sekeres, M. A., Dombret, H., Amadori, S., Wang, J., … QuANTUM-First Study Group (2023). Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet (London, England), 401(10388), 1571–1583. https://doi.org/10.1016/S0140-6736(23)00464-6

[2] Faruqi A, Tadi P. Cytarabine. [Updated 2023 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557680/

The cost effectiveness of telemedicine intervention in terms of chronic disease state management is positive. According to a study on telehealth intervention for chronic disease management, two random, equal-numbered groups of soon-to-be rehospitalized diabetes and/or COPD patients’ spendings on medical care were accessed over the period of 12 months. One group is kept in the traditional setting, and the other group is added with telehealth monitoring intervention. The intervention involved a personalized plan of care. The results show that the intervention group had a significantly lower mean hospital cost (-6553 AUD$), acute admission rate (-4.1 times), and acute admissions cost (-6620 AUD$) compared to the control group. (Bohingamu Mudiyanselage S. et al., 2019) All of those outcomes lead to the conclusion that telemedicine is very cost effective in terms of chronic disease state management. According to the same study, some additional benefits of telemedicines are: patients’ anxiety and depression after telemedicine intervention is generally better; and health literacy is significantly improved with the intervention group. In the anxiety and depression study, the statistics showed significance favoring the intervention group, suggesting patients with depression and anxiety are more likely relieved with their symptoms. In the health literacy study, the statistics showed significance favoring the intervention group, suggesting that their “health-directed behavior; positive and active engagement in life; self-monitoring and insight; constructive attitudes and approaches; social integration and support; and emotional distress” all became better after the 12 month period of study. (Bohingamu Mudiyanselage S. et al., 2019)

[1] Bohingamu Mudiyanselage S, Stevens J, Watts JJ, Toscano J, Kotowicz MA, Steinfort CL, Bell J, Byrnes J, Bruce S, Carter S, Hunter C, Barrand C, Hayles R. Personalised telehealth intervention for chronic disease management: A pilot randomised controlled trial. J Telemed Telecare. 2019 Jul;25(6):343-352. doi: 10.1177/1357633X18775850. Epub 2018 May 24. PMID: 29793387.

Nirsevimab, Beyfortus, is a monoclonal antibody to the respiratory syncytial virus (RSV) fusion protein that requires a single injection administered prior to RSV season. The purpose of Nirsevimab is to prevent hospitalization or medical intervention in infants with those infected with RSV. In a clinical study 1490 randomly assigned infants were grouped in a 2:1 ratio, with 2 receiving the Nirsevimab injection versus one receiving the placebo injection. The clinical study determined that medically attended RSV associated lower respiratory tract infection occurred in less infants in the Nirsevimab group compared to the placebo group. The findings correspond to an efficacy of 74.5%.¹ 

With any new drug or study, monitoring for safety and efficacy is necessary. The study found that some serious adverse events were reported in 6.8% of infants who received Nirsevimab and 7.3% in those who received placebo.¹ The study mostly counted these events as infants that required hospitalization or medical intervention when infected with RSV and did not see that the regimen of Nirsevimab injection could have prevented it. A single adverse event of the Nirvesimab injection that one infant experienced resulted in a grade 3 generalized rash without any systemic features 6 days after the injection. The dose-response relationship is still being explored as researchers observed relatively lower efficacy among infants who were 3.0 months of age or younger or those who weighed less than 5kg.¹  

[1] Hammitt, L. L., Dagan, R., Yuan, Y., Baca Cots, M., Bosheva, M., Madhi, S. A., Muller, W. J., Zar, H. J., Brooks, D., Grenham, A., Wählby Hamrén, U., Mankad, V. S., Ren, P., Takas, T., Abram, M. E., Leach, A., Griffin, M. P., & Villafana, T. (2022). Nirsevimab for prevention of RSV in healthy late-preterm and term infants. New England Journal of Medicine, 386(9), 837–846. https://doi.org/10.1056/nejmoa2110275 

Quizartinib, a selective FLT3 inhibitor, demonstrated improved overall survival in patients with newly diagnosed FLT3-ITD-positive acute myeloid leukemia (AML) when combined with standard chemotherapy, including cytarabine, based on the results from a QuANTUM-First trial. The randomized, double-blind, phase 3 trial included adults aged 18-75 and found a median overall survival of 31.9 months with quizartinib plus chemotherapy compared to 15.1 months with chemotherapy alone. The treatment plan included an initial induction and consolidation phase, during which patients received standard chemotherapy combined with either quizartinib or a placebo. Following this, participants proceeded to a subsequent phase of continuation monotherapy for up to 3 years. 

Considering the trial findings, the patient with newly diagnosed FLT3-ITD-positive AML may be eligible for treatment with quizartinib in combination with cytarabine. The quizartinib plus cytarabine combination therapy, followed by continuation monotherapy, demonstrated superior overall survival compared to chemotherapy alone. Despite this, individual patient factors should be considered when making treatment decisions. Consulting current guidelines and discussing options with the patient may help tailor the treatment approach to the patient’s unique circumstances.

[1] Cortes, J., Perl, A. E., Döhner, H., Kantarjian, H., Martinelli, G., Kovacsovics, T., Rousselot, P., Steffen, B., Dombret, H., Estey, E., Strickland, S., Altman, J. K., Baldus, C. D., Burnett, A., Krämer, A., Russell, N., Shah, N. P., Smith, C. C., Wang, E. S., Ifrah, N., … Levis, M. (2018). Quizartinib, an FLT3 inhibitor, as monotherapy in patients with relapsed or refractory acute myeloid leukaemia: an open-label, multicentre, single-arm, phase 2 trial. The Lancet. Oncology, 19(7), 889–903. https://doi.org/10.1016/S1470-2045(18)30240-7

[2] Erba, H. P., Montesinos, P., Kim, H. J., Patkowska, E., Vrhovac, R., Žák, P., Wang, P. N., Mitov, T., Hanyok, J., Kamel, Y. M., Rohrbach, J. E. C., Liu, L., Benzohra, A., Lesegretain, A., Cortes, J., Perl, A. E., Sekeres, M. A., Dombret, H., Amadori, S., Wang, J., … QuANTUM-First Study Group (2023). Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet (London, England), 401(10388), 1571–1583. https://doi.org/10.1016/S0140-6736(23)00464-6