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Cellulitis and necrotizing fasciitis
Published in Biju Vasudevan, Rajesh Verma, Dermatological Emergencies, 2019
Certain anatomic variants have also been described. Synergistic necrotizing cellulitis is similar to type 1 necrotizing fasciitis and presents as multiple perineal sinuses draining pale “dishwater” exudate containing fragments of necrotic fat [19]. Meleney gangrene is another variant of type I necrotizing fasciitis presenting as necrotic ulcer at postoperative sites, fistulous tracts, or wire-stay sutures [3,20]. Cervical necrotizing fasciitis is another anatomical variant of type 1 necrotizing fasciitis originating from dental or pharyngeal infection, while craniofacial necrotizing fasciitis is caused by group A streptococci following trauma [21]. Fournier gangrene is another genital form of type 1 necrotizing fasciitis involving skin and subcutaneous tissue of genitals, but characteristically sparing the testes, glans penis, and spermatic chord, which have a different blood supply [22,23]. Necrotizing fasciitis when associated with clostridium gangrenous cellulitis may also demonstrate crepitus [3,15].
Efficacy and safety of saxagliptin for the treatment of type 2 diabetes mellitus
Published in Expert Opinion on Pharmacotherapy, 2020
However, in terms of adverse effects, GLP-1R agonists have severe gastrointestinal side effects and SGLT2 inhibitors are associated with an elevated risk of genitourinary tract infections, among which Fournier gangrene is associated with a poor prognosis [110,111]. Based on the characteristics of each class of drugs, DPP-4 inhibitors have the advantage of having fewer and milder AEs, while GLP-1R agonists and SGLT2 inhibitors are favorable in terms of being associated with a reduced incidence of cardiovascular diseases [112]. Taking the pros and cons of each class of drugs into account, a DPP-4i plus SGLT2i combination could be a promising option. Especially, for the case of saxagliptin, combined administration with an SGLT2 inhibitor could be associated with a mitigated risk of heart failure (Table 3) and also a mitigated risk of genitourinary tract infection, a side effect of SGLT2 inhibitors. Moreover, since SGLT2 inhibitor use is associated with a paradoxical increase in endogenous glucose production accompanied by increase of the plasma glucagon level [113,114], administration of a DPP-4 inhibitor, which reduces glucagon secretion, as add-on therapy to a SGLT2 inhibitor is a theoretically reasonable treatment option (Table 3). However, it still remains uncertain how combination therapy might contribute to mitigation of the risk of cardiovascular diseases, including heart failure.
Efficacy and safety profile of SGLT2 inhibitors in patients with type 2 diabetes and chronic kidney disease
Published in Expert Opinion on Drug Safety, 2020
Because of the specific mechanism of action of SGLT2is, leading to increased UGE and osmotic diuresis, some expected adverse effects have been described, such as mycotic genital infections, urinary tract infections (UTIs), volume depletion, and orthostatic hypotension [79]. However, other unexpected concerns were also reported when SGLT2is were prescribed in patients with T2DM such as a higher risk of so-called euglycemic diabetic ketoacidosis episodes. Rare cases of Fournier gangrene were also reported even if a causal relationship remains to be proven [79]. A possible higher risk of lower-limb amputations [80] and bone fractures [81] were identified in an interim analysis of the CANVAS program in 2016. These findings led to specific warnings by both the US Food and Drug Administration (FDA) and the European Medicine Agency (EMA) in 2017.
An update on the safety of SGLT2 inhibitors
Published in Expert Opinion on Drug Safety, 2019
The overall safety profile of SGLT2is is good, with a limited risk of hypoglycemia. Because of the specific mechanism of action leading to increased urinary glucose excretion, a higher risk of mycotic genital infections and UTIs was suspected. A three- to sixfold increase in genital infections was consistently reported, both in RCTs and observational studies, whereas the increase in UTIs appeared almost marginal, with higher risks in women than in men. The risk of volume depletion, including AKI, appears rather low, although caution is recommended in elderly fragile patients who are more commonly exposed to dehydration and orthostatic hypotension. A higher risk of euglycemic DKA is now a well-recognized adverse event linked to SGLT2is. However, despite some studies reported a two-fold increased risk when compared to other GLAs, DKA episodes associated with SGLT2is remain rare in patients with T2DM and occur mainly when patients are exposed to special conditions, especially immediately after surgery. An increased risk of bone fractures has been reported in CANVAS, which resulted in a warning by the FDA for canagliflozin. Other data from meta-analyses of RCTs, other CV outcome trials with empagliflozin and dapagliflozin and observational studies are reassuring, yet the duration of follow-up is probably too short to draw any definite conclusion. Again, a signal for higher risk of LLA was reported in CANVAS. No such signal was mentioned for dapagliflozin and empagliflozin in most RCTs and observational studies. Data with canagliflozin appear more heterogeneous, so that postmarketing surveillance is recommended. The recent warning by the FDA of cases of Fournier gangrene associated with SGLT2i use requires further data, but a higher risk was not recently found in DECLARE-TIMI 58 with dapagliflozin compared to placebo. Overall, the benefits of SGLT2is, especially CV and renal protection, largely outweigh the risks of adverse events, especially in T2DM patients with CV disease.