How Diabetes Medications Affect the Feet

Managing diabetes requires medications that have meaningful effects on foot health — both beneficial (through glucose control) and potentially adverse (through direct side effects). Understanding these medication-foot interactions helps patients and their care teams optimize management and recognize when foot symptoms may have a medication cause. At Balance Foot and Ankle in Howell and Bloomfield Township, Michigan, we review medication lists as part of every diabetic foot evaluation.

Metformin and Vitamin B12 Depletion

Metformin — the most commonly prescribed first-line diabetes medication — reduces intestinal absorption of vitamin B12 when used long-term. B12 deficiency causes a peripheral neuropathy indistinguishable from diabetic neuropathy: burning, tingling, and numbness in the feet. Studies show that 10-30% of long-term metformin users develop B12 deficiency. This means that diabetic patients on metformin with peripheral neuropathy may be experiencing B12 deficiency neuropathy superimposed on (or instead of) diabetic neuropathy. Annual B12 monitoring and supplementation as needed is recommended for metformin users with neuropathy symptoms.

SGLT-2 Inhibitors and Foot Complications

Sodium-glucose cotransporter-2 inhibitors (empagliflozin, dapagliflozin, canagliflozin) reduce glucose by causing urinary glucose excretion. This creates an environment in the urinary tract and genitalia favorable for fungal and bacterial infection — and skin of the foot can also be affected. More seriously, canagliflozin specifically was associated with higher rates of lower extremity amputation in the CANVAS trial (though this association has been questioned with other SGLT-2 inhibitors). SGLT-2 inhibitors are also associated with Fournier’s gangrene (necrotizing fasciitis of the perineum) — a severe warning that applies to diabetic patients who develop any perineal wound.

Thiazolidinediones and Edema

Pioglitazone and rosiglitazone (thiazolidinediones) cause sodium and water retention, producing peripheral edema — bilateral foot and ankle swelling — as a dose-dependent side effect. This edema can worsen existing venous insufficiency, increase infection risk in diabetic foot patients with swollen tissues, and impair wound healing. Patients noticing new or worsening foot swelling after starting a thiazolidinedione should discuss with their prescriber.

Insulin-Related Concerns

Hypoglycemic episodes from insulin can cause the sweating and altered consciousness that contributes to falls and foot injuries. Severe hypoglycemia impairs wound healing and immune function. Injection site lipohypertrophy (lumpy fat accumulation from repeated insulin injection into the same site) can occasionally occur on the thighs or abdomen — not the feet directly — but patients who inject into lipohypertrophic sites have erratic insulin absorption that contributes to glucose variability. Contact Balance Foot and Ankle at (810) 206-1402 for comprehensive diabetic foot evaluation that includes medication review.

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Balance Foot & Ankle — Howell & Bloomfield Township, MI

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Dr. Tom Biernacki, DPM

Dr. Tom Biernacki, DPM is a double board-certified podiatrist and foot & ankle surgeon at Balance Foot & Ankle Specialists in Southeast Michigan. With over a decade of clinical experience, he specializes in heel pain, bunions, diabetic foot care, sports injuries, and minimally invasive surgery. Dr. Biernacki is a member of the APMA and ACFAS, and his patient education content on MichiganFootDoctors.com and YouTube has reached over one million views.