geoffrey modest medical blogs

  A recent study found that GLP-1 receptor agonists were not associated with more acute pancreatitis than sulfonylureas. There was a small increase in GLP-1 related pancreatitis that was offset by decreased alcohol- and triglyceride-related pancreatitis attributable to the GLP-1s: see GLP-1 pancreatitisBMJ2026 in dropbox, or doi:10.1136/ bmjmed-2025-002183 Details : -- 333,687 patients were studied who had type 2 diabetes and antidiabetic therapy was initiated by a GLP-1 receptor agonist (n=132,551) or a sulfonylurea (n= 201,136), between January 2017 and January 2024, from the Veterans Affairs healthcare system databases -- mean age 66, 75% white/21% black -- smoking: never 43%/former 38%/current 20%; alcohol use disorder 6% -- area deprivation index 57 (a composite of socioeconomic disadvantage based on education, income, employment, and other poverty measures, measured at the participants' location, with values ranging from low to high of 0 to 100) -- BMI 34, A1c 8.6%, eGFR 76 -...

  A recent article suggested  that the anti-inflammatory effects of pitavastatin may prevent pancreatic cancer by decreasing pancreatic inflammation (see statin dec pancreat cancer NatCommun2024  in dropbox, or doi.org/10.1038/s41467-024-48441-8)   Details:  -- see commentary below for more of the immunology and potential mechanisms   Results: -- mouse studies assessing chronic inflammation in the skin and pancreas: they created inflammation and fibrosis, documented that IL-33 expression was downstream of a specific signaling (TBK1-IRF-3), and that chronic inflammation depended on IL-33 induction -- they screened an FDA-approved drug library to assess the role of small molecules that would decrease IL-33 expression, finding 5 candidates. -- they found that pitavastatin calcium was an effective suppressant of IL-33 (as well as the bisphosphonate zoledronic acid)     -- pitavastatin suppressed a breast cancer cell line ...

A recent article confirms several other studies suggesting that checking nonfasting lipid levels was as at least as good as getting fasting ones; this study compared results of fasting vs nonfasting from the same individual, looking at clinical outcomes (see  lipids nonfasting ASCOT jamaintmed2019 in dropbox, or doi:10.1001/jamainternmed.2019.0392). Details: -- posthoc perspective follow-up of 8270 participants in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA), comparing nonfasting and fasting lipid levels measured 4 weeks apart in each individual -- Includes both those with cardiovascular disease and those with no prior history -- 82% male, mean age 63, current smoker 35%, BMI 28, blood pressure 165/95, heart rate 71, fasting glucose 115, creatinine 1.1 -- prior stroke 12%, previous peripheral vascular disease 6%, diabetes 30%, family history of premature CHD 23%, aspirin 20% -- median follow-up 3.3...

of all of the new diabetes meds, the one i am most impressed with is exenatide. mostly because the long-acting preparation is injected only once a week, has studies showing it is at least as good an effect as lantus in patients without endstage diabetes, and is pretty physiologic (stimulates postprandial insulin release and decreases appetite, so unusual to be hypoglycemic and tend to lose weight). that being said, none of the new meds have real clinical outcome data, just surrogate marker of A1C improvement (as does rosiglitazone, which we know is associated with increased heart disease). one concern with GLP-1 agonists such as exenitide is that a couple of studies suggested increased risk of pancreatitis, and even some concern about pancreatic cancer. in this light, the FDA and EMA (european medicines agency) independently investigated and came out with a safety assessment (see  dm exenatide and pancreatitis FDA statement 2014  in dropbox, or DOI: 10.10...