Endocrinology

PCP submission

69-year-old hispanic female from Venezuela, who has medical history significant for Type 2 DM diagnosed 10 years ago, hyperlipidemia, hepatic steatosis, hypertension, depressive disorder, urethral instability, and obesity. The patient had treatment with Janumet 50-1000 mg daily, but she has been off the medication for more than a month. The patient has been feeling depressive and is not eating or drinking well. Labs on 4/6/2021 were significant for A1c 11.9%, fasting glucose 194 mg/dL, BUN 39 mg/dL, Cr 1.98 mg/dL, eGFR 25 mL/min/1.73m2, ALK 167 U/L, RBC 5.48, hgb/hct 16.0/49.1; We repeated labs on 4/20/2021: fasting glucose 147 mg/dL, BUN 46 mg/dL, Cr 1.78 mg/dL, eGFR 29 mL/min/1.73m2, serum Na 132 mmol/L. It’s important to document that she showed labs performed in Venezuela on February 2021 and Cr was WNL with positive proteins and glucose in urine (no additional labs to evaluate renal function at that time). Please, see attachment for lab results. Physical exam was positive for decreased foot sensation bilaterally and 1+ dorsalis pulses.

Current Medications:
Tylenol 325 MG Tablet 1 tablet as needed Orally every 4hrs
Vit B12-Methionine-Inos-Chol – Solution as directedIntramuscular
Janumet 50-1000 MG Tablet 1 tablet with meals OrallyTwice a day
Candesartan Cilexetil 16 MG Tablet 1 tablet Orally Oncea day
Aspirin 81 81 MG Tablet Delayed Release 1 tablet OrallyOnce a day

Vital Signs (4/6/2021): Ht 57.5 in, Wt 157 lbs, BMI 33.38 Index, BP 125/80 mm Hg, HR 75 /min, RR 16 /min, Temp 98.1 F

The kidney function is compromised at this point in this non-compliant patient, probably CKD stage 4 (although she had a creatinine WNL in Feb 2021 which does not meet criteria for being < 3 months showing kidney impairment) but U/A continues showing + proteins); but also it can be some acute kidney injury given the fact that the patient is not eating/drinking well and HGB/HCT are increased (hemoconcentration?); although specific gravidity in urine is WNL.
– Janumet was stopped due to decreased eGFR < 30 (because of metformin component);
– We are planning to start Lantus insulin 10 units QHS and continue monitoring fasting glucose to adjust/increase 2 units every 3 days until fasting glucose is between 80-130 mg/dL.
– Would you consider GLP-1 receptor agonist over insulin?
– Would you consider adding SGLT-2 inhibitor in addition to insulin?

Thank you in advance for your attention!

Specialist response

Great questions. Candesartan sounds perfect for her proteinuria. She’s definitely borderline for metformin. If her GFR were to recover to be >30 ml/min, I would consider restarting the metformin at a dose of 500 mg BID. In that case, I would also strongly consider starting an SGLT2 inhibitor, as you mentioned. Label-wise, canagliflozin (100 mg), empagliflozin (10 mg), and dapagliflozin (10 mg) can all be used down to an eGFR of 45 ml/min. Ertugliflozin’s label recommends against its use with a GFR <60 ml/min. KDIGO, though, is comfortable with low-dose SGLT2i use down to a GFR of 30 ml/min. Beware that if you re-check a creatinine within a week or two of starting, you’ll likely see a fall in GFR. It almost always returns to baseline within a few weeks. In the short term, though, I completely agree that insulin is likely to be the mainstay of her treatment. I think starting basal insulin, as you’ve done, and titrating upward to a normal fasting glucose is perfect. If you’d like to be more aggressive, then we could titrate upward according to the old Bergenstal titration, which looks something like: BG <80—> reduce dose by ~2 units BG 81-109—> no change BG 110–139–> +2 units BG 140–179—> +4 units BG >180—> +6 units We tend to titrate every ~48 hours. Our goal is a first-morning fingerstick persistently less than 130 mg/dL. This would buy us some time to make a decision on her other agents. Ideally, if her GFR recovers to >30 ml/min, I’d restart low-dose metformin along with a low-dose SGLT2 inhibitor in addition to her insulin. If her GFR does not recover, I’d offer a GLP-1 agent like semaglutide and titrate it up to the maximum tolerated dose. Either way, I’d also offer Metamucil (psyllium husk) 1 tablespoon daily in water since it appears to lower the A1c by ~0.6%, roughly equivalent to DPP-4 inhibitors like Januvia. I’d also offer a high-potency statin like atorvastatin >/=40 mg or rosuvastatin >/=20 mg daily. I hope that’s helpful. Please message me back if any of this is unclear or incomplete or if new issues come up with your patient’s care.