Ozempic for Adults 65 and Older: Managing the Transition to Adult Care

Does the label treat age 65 and over differently?

The Ozempic label does not give older adults a different starting dose or a lower ceiling [1]. Its Geriatric Use section reports that 744 Ozempic-treated patients (23.6%) in the pooled glycemic-control trials were 65 or older, and that in the cardiovascular outcome trial SUSTAIN 6, 788 (48%) were 65 or older and 157 (9.6%) were 75 or older [1]. The label says no overall differences in safety or efficacy were detected between these patients and younger ones, but greater sensitivity of some older individuals cannot be ruled out [1]. No dose adjustment is recommended for renal impairment, including kidney failure [1].

The label addresses the risks that matter most in this group through its kidney, hypoglycemia, gallbladder and anesthesia warnings rather than through age-based dosing [1].

Dose escalation is where most GI trouble appears

The schedule is fixed: 0.25 mg once weekly for 4 weeks (not a maintenance dose), then 0.5 mg; increase to 1 mg after at least 4 weeks on 0.5 mg, and to 2 mg after at least 4 weeks on 1 mg. The maximum is 2 mg weekly. For the kidney indication, the dose goes to 1 mg after at least 4 weeks on 0.5 mg [1]. A missed dose can be given within 5 days of the missed date; otherwise it is skipped, and the injection weekday can change if the doses are more than 48 hours apart [1].

The label says the majority of reports of nausea, vomiting and diarrhea occurred during dose escalation [1]. In pooled placebo-controlled trials in type 2 diabetes, GI adverse reactions occurred in 15.3% on placebo, 32.7% on 0.5 mg and 36.4% on 1 mg; treatment was stopped for GI reasons in 0.4%, 3.1% and 3.8% respectively; severe GI reactions occurred in 0%, 0.4% and 0.8% [1].

Two label warnings sit close to this. Ozempic is not recommended in patients with severe gastroparesis, and it delays gastric emptying [1]. And the label lists pulmonary aspiration during general anesthesia or deep sedation, with instructions that patients tell healthcare providers about any planned surgery or procedure [1].

Acute kidney injury from fluid loss

Postmarketing reports describe acute kidney injury, in some cases requiring hemodialysis, in patients taking semaglutide. Most of those events occurred in patients who had GI reactions causing dehydration such as nausea, vomiting or diarrhea, and the label says to monitor renal function in patients reporting reactions that could lead to volume depletion, especially during initiation and escalation [1]. A handoff note should carry current renal-function results and any gastrointestinal symptoms that could cause volume depletion [1].

Hypoglycemia when insulin or a sulfonylurea is on board

Ozempic stimulates insulin release in the presence of elevated blood glucose, so combining it with insulin or an insulin secretagogue such as a sulfonylurea raises hypoglycemia risk, including severe hypoglycemia. The label says to consider reducing the dose of the insulin secretagogue or insulin when starting Ozempic [1].

In the 30-week trial of Ozempic added to basal insulin with or without metformin, documented symptomatic low glucose at or below 70 mg/dL occurred in 15.2% on placebo, 16.7% on 0.5 mg and 29.8% on 1 mg; severe episodes requiring the assistance of another person occurred in 0%, 0% and 1.5% [1]. The label notes that hypoglycemia was more frequent when Ozempic was used with a sulfonylurea [1]. When Ozempic is given with insulin, the two are separate injections that are never mixed; the same body region is acceptable but not adjacent sites [1].

Kidney outcomes: FLOW and the current indication

Ozempic is indicated to reduce the risk of sustained eGFR decline, end-stage kidney disease and cardiovascular death in adults with type 2 diabetes and chronic kidney disease [1]. The trial behind that indication, FLOW, enrolled 3,533 adults with type 2 diabetes and CKD who received 1 mg weekly or placebo, with median follow-up of 3.4 years and an early stop at a planned interim analysis. The composite of kidney failure, 50% or more eGFR decline, or kidney or cardiovascular death occurred in 18.7% on semaglutide versus 23.2% on placebo (hazard ratio 0.76, 95% CI 0.66 to 0.88); all-cause death was 12.8% versus 15.8% (hazard ratio 0.80) [2]. Benefit was not evident in the few patients taking an SGLT2 inhibitor at baseline [2].

Which cardiovascular trial belongs to which product

Ozempic's cardiovascular indication in adults with type 2 diabetes and established cardiovascular disease rests on SUSTAIN 6, which randomized 3,297 adults with type 2 diabetes to 0.5 mg or 1 mg weekly or placebo for 104 weeks. The composite of cardiovascular death, nonfatal heart attack or nonfatal stroke occurred in 6.6% versus 8.9% (hazard ratio 0.74, 95% CI 0.58 to 0.95) [3].

SELECT is a different product. It tested the Wegovy dose of 2.4 mg, not Ozempic, in 17,604 adults aged 45 or older with established cardiovascular disease and a BMI of 27 or more but no diabetes; the same three-part composite occurred in 6.5% versus 8.0% (hazard ratio 0.80, 95% CI 0.72 to 0.90) over a mean follow-up of 39.8 months [4]. Ozempic has no weight-loss indication; weight management is the Wegovy indication [1].

What should travel with the patient at a handoff

Points drawn from the label's own instructions:

• The current dose and the date of the last injection, which the label's missed-dose rule (within 5 days, otherwise skip) refers to [1].
• Who gives the injection, since Ozempic pens must never be shared between patients, even with a new needle [1].
• Whether insulin or a sulfonylurea is also prescribed, and at what dose, because the label advises considering a reduction when Ozempic starts [1].
• Recent kidney function and fluid status, because the label advises monitoring renal function when GI reactions could cause volume depletion [1].
• Any planned surgery or deep sedation, because of the aspiration warning [1].

Boxed warning: thyroid C-cell tumors

Semaglutide caused thyroid C-cell tumors in rodents at clinically relevant exposures, and whether it does so in humans is unknown. The drug is contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2, and the label says routine calcitonin monitoring or thyroid ultrasound is of uncertain value [1].