5 unexpected side effects of Ozempic use

By Alpana Mohta, MD, DNB, FEADV, FIADVL, IFAAD | Fact-checked by Barbara Bekiesz
Published November 20, 2024

Key Takeaways

  • While semaglutide has a few known side effects, some surprising effects benefit your patients’ health far beyond glycemic control.

  • For the right patients, the drug’s many beneficial side effects may mean fewer meds overall and better outcomes across the board.

The US shelled out a whopping $38.6 billion on semaglutide (Ozempic, Wegovy, and Rybelsus) in 2023, with even higher projections anticipated for 2024.[] With such widespread use, it’s no surprise to see a dizzying array of side effects—both negative (from hair loss to gallstones) and positive (from improved heart health to pain relief).

To sum up a record-breaking year for the pharmaceutical companies who manufacture semaglutide drugs, let’s take a closer look at the top-five most surprising beneficial side effects of Ozempic.

Better-than-anticipated effects for kidney disease

As semaglutide has shown strong results for diabetes, it wasn’t surprising to see benefits in diabetic patients with chronic kidney disease (CKD). But the results turned out to be even better than anticipated. In the recent FLOW trial (a randomized, double-blind study of 3,533 participants), semaglutide reduced the risk of major kidney events by 24% over a median follow-up of 3.4 years compared to placebo.[] Patients receiving semaglutide also had a slower decline in kidney function and a 20% reduction in all-cause mortality. 

The outcomes were so compelling that Novo Nordisk, the drug’s manufacturer, ended the trial early following a recommendation from the data safety board, which deemed it unethical to continue with a placebo group given the substantial benefits observed.[]

Related: Is Ozempic the 'biggest thing since penicillin'? Physicians weigh in

The exact mechanisms aren’t fully understood, but it’s believed that semaglutide’s anti-inflammatory properties, improvements in endothelial function, and possible direct kidney protection are major factors. 

Reduced cravings for addictive substances

Many patients using a GLP-1 report a reduction in cravings for substances like alcohol and nicotine; consider the following:

  • A 2024 study spanning 1.3 million patients across the US showed a 50% decrease in alcohol abuse and a 40% reduction in opioid overdoses among users of GLP-1 drugs.[]

  • Another study involving 83,000 obese patients reported a 50%–56% lower incidence of alcohol use disorder among those on semaglutide compared with those on other anti-obesity medications.[]

  • Similar results were replicated in a cohort of nearly 600,000 type 2 diabetes patients.[]

The proposed mechanism involves semaglutide’s influence on the brain’s dopamine reward system, like the ventral tegmental area and nucleus accumbens, where it may attenuate the rewarding effects of alcohol and other substance abuse drugs. Delayed gastric emptying, another effect of semaglutide, may also contribute by slowing alcohol absorption and lessening its rewarding impact.[]

Related: Ozempic curbs more than just appetite

Pain relief

Semaglutide affects inflammation by acting over the GLP-1 receptors in T-cells involved in immune responses.[] Both preclinical and clinical studies indicate that the drug downregulates pro-inflammatory cytokines, including TNF-alpha and IL-6, which could help lower systemic inflammation. 

Though we still lack robust clinical data, a promising trial across 11 countries recently published in The New England Journal of Medicine showed that semaglutide’s pain relief in obesity-related knee osteoarthritis was significantly higher than placebo.[]

Related: New study links Ozempic to sharp reduction in osteoarthritis knee pain

Neuroprotection

While a few disease-modifying treatments exist for Alzheimer’s disease (AD), no such therapies are available for Parkinson’s disease (PD). Animal studies strongly suggest a neuroprotective role for GLP-1RAs. 

In PD models, semaglutide has been shown to enhance mitochondrial function, reduce dopaminergic neuron loss, and improve motor function.[] Similarly, AD models treated with GLP-1s displayed reduced amyloid-beta plaques, lower neuroinflammation, and improved learning and memory.

Although semaglutide does not readily cross the blood-brain barrier, it concentrates in the hypothalamus, which may contribute to central effects. Human trials are currently underway to explore semaglutide's potential in managing AD and PD further.[]

Related: Could Ozempic slow Alzheimer’s progression?

Improved heart health

The cardiovascular benefits of semaglutide are well-documented in patients with type 2 diabetes, with a consistent track record of reduction in heart failure and other cardiovascular events. However, what’s intriguing is that these effects appear to occur independently of weight loss and blood sugar control.[]

GLP-1 receptors are present in vascular endothelium and myocardium, suggesting that the drug might work directly on cardiac tissue to reduce fibrosis, improve blood flow, and mitigate the progression of atherosclerosis. One proposed mechanism for semaglutide’s cardioprotective actions is its anti-inflammatory potential. Consider the following:

  • A 2024 meta-analysis of 13 clinical trials involving over 26,000 patients showed that semaglutide significantly reduced C-reactive protein (CRP) levels compared to placebo and other glucose-lowering drugs, independent of diabetes status.[]

  • In a multicentric placebo-controlled trial of obese cardiovascular patients without diabetes, cardiovascular benefits with semaglutide began to appear early after treatment initiation, even before the full magnitude of weight loss set in.[]

Related: New weight-loss drugs yield cardiovascular benefits—along with adverse effects

What this means for you

For doctors, these added benefits of semaglutide open up new possibilities. When choosing treatment for patients with diabetes or obesity, knowing that semaglutide might also curb cravings, ease inflammation, and protect the heart, brain, and kidneys could help make it a go-to option. For the right patients, this might mean fewer meds overall and better outcomes across the board.

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