52% is nothing to worry about if you don’t have elevated platelets. You need to be sure to drink a decent amount of water prior to a blood draw. If you don’t, your hematocrit will be significantly higher than it would otherwise be. Let’s say for instance you get blood drawn in the evening after a full day of eating, your hematocrit will be at its lowest. In any case, 52% is nothing when you have people with hematocrit up to 70% for years with no issues at the highest altitude in the world. There is absolutely zero reason to think a slightly elevated hematocrit from a SGLT2 will magically be worse than people living at high altitudes who also have secondary erythrocytosis (though I will argue that you don’t). Don’t lose one second of sleep over it.
@Davin8r doesn’t agree with me on this topic for the record and that’s okay. We already went back and forth on it earlier.
I am about to start empagliflozen. Can you remind me what test I should get before starting in order to have baseline data to monitor? I saw hematocrit mentioned above, anything else?
I am not diabetic. I have been taking metformin for years and plan to drop it. All advice welcome.
From OpenEvidence: Individuals with high hematocrit due to high altitude are protected from thrombosis compared to those with high hematocrit resulting from testosterone replacement therapy or other medications because high-altitude erythrocytosis is not associated with a hypercoagulable or hypofibrinolytic state, whereas medication-induced erythrocytosis is often accompanied by prothrombotic changes.
In high-altitude dwellers…chronic hypoxia-induced erythrocytosis is accompanied by adaptive vascular and rheological changes that mitigate the risk of thrombosis, including normalization of vascular shear stress and blood pressure, and altered peripheral vascular function.[3]
In contrast, testosterone therapy and other medications that induce erythrocytosis are associated with increased risk of venous thromboembolism (VTE), likely due to increased blood viscosity, platelet activation, and prothrombotic changes. Large pharmacoepidemiologic studies and clinical guidelines from the Endocrine Society indicate that testosterone-induced erythrocytosis is an independent risk factor for VTE and major adverse cardiovascular events, especially in the first year of therapy.[4-6] The Endocrine Society recommends monitoring hematocrit and withholding testosterone therapy if hematocrit exceeds 54% due to these risks.[5]
Thus, the key difference lies in the underlying pathophysiology: high-altitude erythrocytosis is accompanied by protective vascular adaptations and a non-prothrombotic hemostatic profile, while medication-induced erythrocytosis is associated with increased thrombotic risk due to altered blood rheology and procoagulant changes.[1-3][6]
Yeah, normally I wouldn’t care too much about the number but lately I have been waking up with some headaches/queasiness/aches so I’m concerned. Is it due to elevated HCT? Can’t say for sure. I lowered my dose and might donate a Double Red just to cover my bases and bring HCT back to baseline to see.
Among new SGLT2i users, 3255 cases of depression occurred (7.18 per 1000 person-years) versus 7190 cases among DPP4i users (10.12 per 1000 person-years). After adjustment for demographic and clinical covariates, SGLT2i use was consistently associated with a lower risk of depression in both the full cohort (adjusted HR = 0.77; 95% CI: 0.73–0.80) and the propensity score–matched cohort (adjusted HR = 0.77; 95% CI: 0.74–0.81). The association remained robust in multiple sensitivity analyses and across clinical subgroups.
Abstract Background: Growing evidence are showing beneficial effects of sodium glucose transport protein 2 inhibitors (SGLT2i) in treatment of heart failure, but underlying neurogenic mechanism remains unclear. In this study the effect of empagliflozin (EM) on sympatho-excitation and potential neurogenic mechanism for EM’s therapeutic effects on cardiac remodeling were studied.
Methods: Deoxycorticosterone acetate (DOCA)-salt and high-salt (8%) diet (HSD) mouse models were utilized. Single-cell RNA sequencing was used to explore the mechanism by which SGLT2 inhibitors improve cardiac remodeling in hypertension. Meanwhile, blood samples were collected from hospitalized patients diagnosed with heart failure to verify the results of animal studies.
Results: In DOCA-salt or HSD treated mice, EM was associated with a protective, blood pressure-independent effect on cardiac remodeling. Both DOCA-salt and HSD induced sympatho-excitation, together with neuronal hyper-activity in the pre-autonomic regions of brain, and these were blunted in mice with EM co-treatment. Additionally, single-nucleus RNA sequencing using hypothalami indicated that cellular interplays among the vessels, microglia and inhibitory neurons were involved in the disease- and EM-associated actions. Further analysis of microglia pinpointed a close involvement of peripheral immune activation in disease-associated state transformation of microglia, during DOCA-salt or HSD treatment, including increased lymphocytes count and plasma level of interferon-γ. Differentially expressed genes in neurons highlighted that EM abolished disease-associated upregulation of protein ubiquitination, which might support imbalance of presympathetic excitatory/inhibitory tones, and vasopressin production. In patients’ blood samples, EM was associated with significant elevation of hematocrit value in all groups, and reduction of lymphocytes counts in the patients with high NT-proBNP value (> 2550 pg/mL, no diuretic co-treatment).
Conclusions: Our data provide a neuro-immune pathway by which EM blunts disease-associated cardiac sympathetic tone and hypertrophic remodeling.
Popular Oral Drug for Diabetes May Hold ‘Intriguing’ Side Benefit
— Study finds lower arthritis risk with SGLT2 inhibitors, but number needed to treat was large
Key Takeaways
In a study from Korea, adults with type 2 diabetes had a lower risk for autoimmune rheumatic diseases after starting an SGLT2 inhibitor rather than a sulfonylurea.
Over 15,000 adults would need to be treated with an SGLT2 inhibitor to prevent one autoimmune rheumatic disease, the researchers found.
The lower risk was driven by fewer cases of inflammatory arthritis, and not connective tissue disease.
Chinese preprint