What the warning describes
Section 5.5 of the US label covers acute kidney injury due to volume depletion. There have been postmarketing reports of acute kidney injury in people on Victoza®, in some cases requiring haemodialysis, and in most of them the person had become dehydrated through nausea, vomiting or diarrhea. [1] The label asks prescribers to monitor kidney function in patients reporting such reactions, especially when starting Victoza® or increasing the dose. [1] Its postmarketing list adds acute kidney failure, worsening of chronic kidney failure and raised serum creatinine. [1]
Europe lists kidney impairment and acute kidney failure as uncommon, between 1 in 1,000 and 1 in 100 people, and dehydration as uncommon too. [2] Canada says some of these events occurred in people without known kidney disease and asks for caution in anyone who becomes dehydrated. [3]
The stomach reactions involved
The three reactions linked to fluid loss are the most common side effects of Victoza®. [1] All three were more frequent on liraglutide than on placebo in the pooled adult trials, and digestive reactions were most likely during the first two to three months. [1] Europe adds that people with mild or moderate kidney impairment may have more digestive effects on liraglutide. [2]
| Reaction | Placebo (661) | Liraglutide 1.2 mg (645) | Liraglutide 1.8 mg (1,024) |
|---|---|---|---|
| Nausea | 5% | 18% | 20% |
| Diarrhea | 4% | 10% | 12% |
| Vomiting | 2% | 6% | 9% |
People who already have kidney disease
No dose adjustment of Victoza® is recommended for kidney impairment. [1] A 26-week trial included people with moderate kidney impairment, and in LEADER 41.4% of those on Victoza® had mild, 21.4% moderate and 2.5% severe impairment at the start, with no overall differences in safety or efficacy compared with normal kidney function. [1] In that 26-week trial, HbA1c fell by 1.05% on liraglutide against 0.38% on placebo, and the safety profile was similar to other studies. [2]
The US label says experience in end-stage kidney disease is limited. [1] Europe states there is no therapeutic experience and does not recommend Victoza® for these patients. [2] Liraglutide is not cleared mainly by the kidneys: blood levels were on average 19% to 35% lower in people with kidney impairment than in healthy volunteers. [1]
What LEADER found for the kidneys
LEADER reported a prespecified kidney outcome: new persistent heavy albumin loss in the urine (macroalbuminuria), doubling of creatinine, end-stage kidney disease or kidney death. Over a median 3.84 years, it occurred in 268 of 4,668 people on liraglutide and 337 of 4,672 on placebo, a hazard ratio of 0.78. [4] The difference came mainly from fewer new cases of macroalbuminuria, 161 against 215. [4] Kidney adverse events overall were similar, 15.1 against 16.5 per 1,000 patient-years, and so was acute kidney injury, 7.1 against 6.2. [4] Europe reports the same nephropathy hazard ratio in its product information. [2]
This was a secondary outcome in a cardiovascular trial, and the US label does not list kidney protection as a reason to prescribe Victoza®. [1] It does suggest that, in people at high cardiovascular risk, the fluid-loss warning sits alongside a longer-term kidney picture that was not worse on liraglutide.
Why it might happen
Label-supported chain: nausea, vomiting or diarrhea lead to fluid loss, which can reduce blood flow to the kidneys and cause acute injury. [1] MedlinePlus lists dehydration among the causes of acute kidney failure. [6]
Single-case evidence: a 2012 case report described a 53-year-old woman who started liraglutide 1.8 mg, had weeks of worsening stomach symptoms and weight loss, and developed acute kidney injury with damage to the kidney tubules on biopsy; she needed dialysis and recovered after stopping liraglutide and receiving fluids. [5] A single case can raise a question but cannot show how often this happens.
Other kidney risks in type 2 diabetes
NIDDK describes diabetes as the leading cause of kidney disease and says about 1 in 3 adults with diabetes has it, usually without symptoms. [8] It recommends yearly urine albumin and blood tests for people with type 2 diabetes. [8] MedlinePlus lists other causes of acute kidney injury, including anti-inflammatory painkillers, some antibiotics and blood pressure medicines, contrast dye for scans, very low blood pressure and urinary blockage. [6] Several of these are common in people taking Victoza®.
What the sources ask of patients
- Drink fluids to help avoid dehydration, especially while starting treatment, as the Medication Guide and EU leaflet ask. [1][2]
- Tell your provider promptly about nausea, vomiting or diarrhea that keeps going, and about signs of kidney injury. [1]
- Before starting, tell your provider about kidney problems and severe vomiting, diarrhea or dehydration, as the Canadian patient information asks. [3]
- Mention Victoza® when a new medicine is added, especially an anti-inflammatory painkiller, or before a scan with contrast. [6]
- Keep up the yearly kidney checks NIDDK recommends for type 2 diabetes. [8]
Victoza® is a registered trademark of Novo Nordisk A/S. PepLabo is not affiliated with or endorsed by Novo Nordisk A/S.
When to get help
| Sign | Who to contact | How fast | Source |
|---|---|---|---|
| Confusion, fainting or no urine after repeated vomiting or diarrhea | Emergency services (911 or local number) | Emergency | MedlinePlus [7] |
| Passing much less urine, or swelling of the legs, ankles or feet | Stop Victoza® and call your provider | Today | MedlinePlus liraglutide [9]; MedlinePlus [6] |
| Nausea, vomiting or diarrhea that does not stop | Your provider, the same day | Today | Medication Guide [1] |
| Dark urine, thirst, dry mouth or dizziness | Drink fluids and contact your provider if it does not improve | Today | MedlinePlus [7] |
| A rise in creatinine on a routine blood test | Discuss with your prescriber | At your next appointment | US label sections 5.5 and 6.2 [1] |
