On Mar 13, 2021, at 7:41 AM, Eleanor Kellon, VMD <drkellon@...> wrote:

We have had our first case of a presumed adverse reaction to Invokana, hypertriglyceridemia. The first thing noticed was a rapid weight loss, slight decrease in hay consumption assumed at the time to be because he didn't like a new hay being introduced. Appetite for cubes and supplements was, and remained, normal. Dehydration and inadequate calorie intake were ruled out, Thyro-L supplement was stopped and he looked like he might be gaining back a little weight but became lethargic, 'disoriented'/weak (wish they could talk!) and uncomfortable resembling colic but unresponsive to treatment. Blood work revealed severe lipemia and he was hospitalized; currently responding well to stopping Invokana and treatment. In retrospect, this is entirely consistent with hyperlipemia. Hyperlipemia has not been reported as a side effect of Invokana in other species.

Some degree of hyperlipidemia can accompany IR with EMS or PPID. It is most common in ponies, minis and donkeys but alterations in fats also occur in full size horses. The reason is the reduced availability of glucose because of IR causes a release of triglycerides from fat stores as an alternative energy source. In horses, the glycerol backbone of the triglycerides is converted to glucose. However, glucose is the pivotal energy source and is needed to generate some of the intermediates in the Krebs cycle where the fats are burned. The body normally relies on stored glycogen as a glucose source in time of shortage but this supply is limited and already impaired with IR. The backbones of some amino acids can be converted to glucose so protein breakdown will also occur. However, considerable energy has to be used to make that conversion so it's not very efficient.

What likely happened in the Invokana case above is the horse was losing so much glucose in his urine that the body could not keep up. Maintaining normal blood glucose for the heart and brain is survival priority #1. The horse was essentially thrown into a state of starvation which triggered the triglyceride release. This is not seen in other species but the low sugar and starch diet we feed may have something to do with this.

Lessons to be learned here are:

• Triglycerides should be added to the screening and monitoring of all horses on Invokana - prior to starting, and at 1 and 2 months after starting; sooner if the signs below are witnessed. Note: Having mildly elevated triglycerides does not automatically mean Invokana cannot be used. We have also seen triglycerides improve on Invokana.
• Check triglycerides if you notice unexplained weight loss, altered appetite, lethargy, 'depression' or other altered mental status, weakness

Eleanor in PA

www.drkellon.com 
EC Owner 2001