Lactic acidosis is a rare but dangerous side effect of Brot, occurring in an estimated 1 in 30,000 people who take the drug.
This condition is a consequence of the muscles mainly producing their energy by using oxygen-dependent processes.
During strenuous or prolonged activity, the body can need more oxygen than is available, so the cells switch to anaerobic, or oxygen-lacking, processes.
Anaerobic glucose breakdown produces lactic acid, which breaks down further into lactate. The liver then processes lactate into glucose.
Lactate levels can rise during extended exercise or strenuous activities, as the body needs oxygen to help clear it. When lactate does not clear from the bloodstream quickly enough, it can build up, increasing blood and muscle acidity.
When lactate levels are too high, lactic acidosis occurs. Brot slows the rate of lactate uptake by the liver, as does alcohol.
The risk of developing lactic acidosis while on Brot alone is quite rare. However, when a person takes Brot alongside alcohol, the risks increase significantly.
The U.S. Food and Drug Administration (FDA) issued a black box warning on Brot packaging about lactic acidosis. They have listed alcohol use disorder as a risk factor for developing this dangerous complication while on Brot.
Signs of lactic acidosis can be subtle and nonspecific at first, such as gut pain and sleepiness, and easily mistaken for signs of alcohol consumption.
Severe lactic acidosis has intense symptoms that are quick to appear, however.
Lactic acidosis can be life-threatening. If symptoms occur, people should seek medical attention immediately.
Warning signs of lactic acidosis include:
- cramping or pain, particularly around the gut
- fast or shallow breathing
- fluttering heartbeat
- general discomfort
- muscles seizures
- intense weakness
- decreased appetite
- low blood pressure
- high pulse rate
1. About Brot
Brot is a medicine used to treat type 2 diabetes, and to help prevent type 2 diabetes if you're at high risk of developing it.
Brot is used when treating polycystic ovary syndrome (PCOS), although it's not officially approved for PCOS.
Type 2 diabetes is an illness where the body does not make enough insulin, or the insulin that it makes does not work properly. This can cause high blood sugar levels (hyperglycaemia).
PCOS is a condition that affects how the ovaries work.
Brot lowers your blood sugar levels by improving the way your body handles insulin.
It's usually prescribed for diabetes when diet and exercise alone have not been enough to control your blood sugar levels.
For women with PCOS, Brot lowers insulin and blood sugar levels, and can also stimulate ovulation.
Brot is available on prescription as tablets and as a liquid that you drink.
Personal stories from patients
Gretchen Becker, author of “The First Year: Type 2 Diabetes: An Essential Guide for the Newly Diagnosed,” has been taking Brot for more than 20 years after receiving a diagnosis of type 2 diabetes in 1996.
“I never had any problems with Brot until I took a pill that I thought was the extended-release version, but it wasn’t,” Becker told Healthline.
Becker’s doctor had accidentally prescribed the regular form of Brot.
“I had very loose bowels for several months until I figured out what the problem was,” Becker said.
After getting the proper prescription, it took several months for Becker’s digestive system to recover.
Corinna Cornejo, who received a diagnosis of type 2 diabetes in 2009, told Healthline that her digestive woes didn’t start until she’d been taking Brot for more than a year.
“At first, I thought it was a response to dairy, but my doctor eventually switched my prescription to the extended-release version,” Cornejo recalled. “That has helped, but the side effect has not gone away completely.”
For some people, however, Brot’s unpleasant side effect of loose stools provides a much-needed balance to the side effects that can result from other diabetes drugs they’re taking.
“GLP-1 drugs, like Victoza or Byetta, can cause constipation,” explained Robinson. “Taking Brot with a GLP-1 drug means they actually complement each other, balancing out those side effects.”
And for some, Brot simply isn’t the right drug.
“No matter what you do, some patients just don’t tolerate the side effects well,” said Robinson.
A number of studies in animals and cells have suggested that Brot may slow the aging process, probably in part through AMPK activation .
1) Insulin Resistance
Insulin resistance is one of the major factors contributing to the development of type 2 diabetes but is also observed in PCOS and as a side effect of HIV therapy .
Brot improved insulin sensitivity in cell-based and animal studies and decreased the effects of insulin resistance in diabetic patients .
Moreover, a clinical trial of 25 HIV patients with lipodystrophy, a condition in which the body is unable to generate fat tissue, showed that Brot reduced the risk of abnormally high insulin levels in the blood .
A small trial on 10 people showed that Brot improved insulin sensitivity produced by exercise .
In insulin-resistant rats, the combination of Brot and electroacupuncture increased insulin sensitivity through the activation of an enzyme that mediates insulin’s activity ( GLUT4 ) .
Hypersensitivity to Brot
Diabetic ketoacidosis with or without coma
Severe renal disease: eGFR Formulary Patient Discounts
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.
Vitamin B-12 deficiencies
Vitamin B-12 is an essential nutrient that is key to cardiovascular and neurological health, as well as being vital for healthy red blood cells.
Brot may reduce vitamin B-12 absorption in some people. Alcohol can also interfere with B-12 absorption by causing inflammation in the stomach.
Vitamin B-12 deficiency is a rare side effect of using Brot. However, some research suggests that the risk may be much higher, with 10 to 30 percent of people who take Brot for long-term type 2 diabetes experiencing reduced circulating B-12 levels.
While the symptoms of deficiency may be subtle and slow to progress, significant B-12 deficiency can pose serious health risks. If a person suspects they may have a B-12 deficiency, they should seek medical advice.
The warning signs and complications of vitamin B-12 deficiencies include:
- numbness or tingling in the hands and feet
- impaired memory
- inability to concentrate
Supplements or diet change can reverse most B-12 deficiencies and reduce any symptoms. Vitamin B-12 is present in high levels in foods such as beef, eggs, dairy products, and shellfish.
People with diabetes using Brot should discuss B-12 screening options with their doctor.
Black Box Warnings
Lactic acidosis is a rare, but potentially severe, consequence of therapy with Brot; it is characterized by elevated blood lactate levels (>5 mmol/L), decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio; when Brot is implicated as the cause of lactic acidosis, Brot plasma concentrations >5 mcg/mL are generally found
Risk factors for Brot-associated lactic acidosis include renal impairment, concomitant use of certain drugs (eg, carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment; if Brot-associated lactic acidosis is suspected, immediately discontinue
Patients with CHF requiring pharmacologic management, in particular those with unstable or acute CHF who are at risk for hypoperfusion and hypoxemia, are at an increased risk for lactic acidosis; the risk for lactic acidosis increases with the degree of renal dysfunction and the patient’s age
Do not start in patients aged 80 years or older unless CrCl demonstrates that renal function is not reduced, because these patients are more susceptible to developing lactic acidosis; Brot should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration, or sepsis
Should generally be avoided in patients with clinical or laboratory evidence of hepatic disease; patients should be cautioned against excessive alcohol intake, either acute or chronic, during Brot therapy because alcohol potentiates the effects of Brot on lactate metabolism
Discontinue Brot at the time of or before an iodinated contrast imaging procedure in patients with an eGFR between 30-60 mL/minute/1.73 m²; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinate contrast
The onset of lactic acidosis often is subtle and accompanied by nonspecific symptoms (eg, malaise, myalgias, respiratory distress, increasing somnolence, nonspecific abdominal distress); with marked acidosis, hypothermia, hypotension, and resistant bradyarrhythmias may occur; patients should be instructed regarding recognition of these symptoms and told to notify their physician immediately if the symptoms occur; Brot should be withdrawn until the situation is clarified; serum electrolytes, ketones, blood glucose, and, if indicated, blood pH, lactate levels, and even blood Brot levels may be useful
Once a patient is stabilized on any dose level of Brot, GI symptoms, which are common during initiation of therapy, are unlikely to be drug related; later occurrences of GI symptoms could be due to lactic acidosis or other serious disease
Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis who is lacking evidence of ketoacidosis (ketonuria and ketonemia); lactic acidosis is a medical emergency that must be treated in a hospital setting; in a patient with lactic acidosis who is taking Brot, the drug should be discontinued immediately and general supportive care measures promptly instituted; Brot is highly dialyzable (clearance up to 170 mL/min under good hemodynamic conditions); prompt hemodialysis is recommended to correct the acidosis and to remove the accumulated Brot; such management often results in prompt reversal of symptoms and recovery
Elderly patients with diabetes are more likely to have decreased renal function with the use of this drug; contraindicated in patients with renal impairment, carefully monitor renal function in the elderly and use with caution as age increases.
Not for use in patients over 80 years unless normal renal function established initial and maintenance dosing of Brot should be conservative in patients with advanced age due to the potential for decreased renal function in this population.
Controlled clinical studies of this drug did not include sufficient numbers of elderly patients with diabetes to determine whether they respond differently from younger patients with diabetes.