instalment 10: more prescription medications that may be helpful in certain situations

Liraglutide

Liraglutide is one of a family of medications collectively referred to as glucagon-like peptide-1 receptor agonists, also known as GLP-1 receptor agonists or incretin mimetics. This Wikipedia article talks about the other medications in this class by both their generic and their trade names. These drugs are given by subcutaneous injection, typically once daily. In spite of this inconvenience, they are touted for improving blood sugar control in patients with type 2 diabetes, based on their ability to increase insulin secretion.

You should now be asking: wait a minute! If these medications increase insulin secretion, how could they be helpful in inflammation? Haven’t you been telling us that higher insulin causes all sorts of problems, including inflammation?

Good for you for raising that important point! I have a complicated answer. Complicated because I suspect that the pharmaceutical industry really does not want you to know that insulin reduction is the way to go. So here is my explanation.

GLP-1 receptors are found all over, including in the brain. So while it’s very true that GLP-1 receptor agonists like liraglutide increase insulin secretion by pancreatic beta-cells in response to glucose, it’s also true that gastric GLP-1 receptors cause a slowing of gastric emptying1, and receptors in the brain cause a decrease in appetite and a lowering of food intake2, with possibly a selective reduction of protein intake3. This reduction in energy intake is almost certainly the cause of the well-documented weight reduction4 found with these medications. And of course, less food means overall less insulin, and less protein means less IGF-1. So, we have a possible mechanism to explain the anti-inflammatory effect of medications like liraglutide5.

So if you have type 2 diabetes and are taking insulin, talk to your doctor about whether these drugs may be an alternative for you, given the risks associated with insulin therapy6.

But caution is warranted! It is possible that these medications might stimulate pancreatic cancer. They just haven’t been around for long enough to know for sure.

Acarbose

Dietary starch consists of glucose molecules strung together; for the glucose to be absorbed, starches must be broken down by the action of an enzyme called alpha-glucosidase. Acarbose and similar medications miglitol and voglibose inhibit this enzyme, thus reducing the amount of glucose which gets absorbed and thereby reducing the amount of insulin which gets secreted. That might account for the known anti-inflammatory effect of acarbose7, but probably more important is what happens to the starch that doesn’t get broken down. As I discussed in a previous instalment about nondigestible fibre, the undigested starch can be fermented by gut bacteria to produce short-chain fatty acids (SCFAs)8, especially butyrate, which are anti-inflammatory.

Finally, while starch has an energy content of 4 kilocalories per gram, when that same amount of starch is instead absorbed as SCFAs it provides only about 1.5 kilocalories per gram. So these medications certainly have the potential to help with losing weight9.

So that is the last of the specific do-it-yourself interventions that I had listed in the introductory “Short Take”. In the next instalment, I will explain how and why the non-specific “don’t stress about stress” dictum can be helpful.

  1. Jelsing J, Vrang N, Hansen G, Raun K, Tang-Christensen M, Knudsen LB. Liraglutide: short-lived effect on gastric emptying — long lasting effects on body weight. Diabetes Obes Metab. 2012;14:531-538. PMID 22226053
  2. Costa A, Ai M, Nunn N et al. Anorectic and aversive effects of GLP-1 receptor agonism are mediated by brainstem cholecystokinin neurons, and modulated by GIP receptor activation. Mol Metab. 2021;55:101407. PMID 34844019
  3. Peters CT, Choi YH, Brubaker PL, Anderson GH. A glucagon-like peptide-1 receptor agonist and an antagonist modify macronutrient selection by rats. J Nutr. 2001;131:2164-2170. PMID 11481412
  4. van Can J, Sloth B, Jensen CB, Flint A, Blaak EE, Saris WH. Effects of the once-daily GLP-1 analog liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese, non-diabetic adults. Int J Obes (Lond). 2014;38:784-793. PMID 23999198
  5. Lee YS, Jun HS. Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control. Mediators Inflamm. 2016;2016:3094642. PMID 27110066
    Bray JJH, Foster-Davies H, Salem A et al. Glucagon-like peptide-1 receptor agonists improve biomarkers of inflammation and oxidative stress: A systematic review and meta-analysis of randomised controlled trials. Diabetes Obes Metab. 2021;23:1806-1822. PMID 33830637
  6. Currie CJ, Poole CD, Evans M, Peters JR, Morgan CL. Mortality and other important diabetes-related outcomes with insulin vs other antihyperglycemic therapies in type 2 diabetes. J Clin Endocrinol Metab. 2013;98:668-677. PMID 23372169
  7. Lin YC, Chen YC, Hsiao HP et al. The effects of acarbose on chemokine and cytokine production in human monocytic THP-1 cells. Hormones (Athens). 2019;18:179-187. PMID 30827017
  8. Xu GD, Cai L, Ni YS et al. Comparisons of Effects on Intestinal Short-Chain Fatty Acid Concentration after Exposure of Two Glycosidase Inhibitors in Mice. Biol Pharm Bull. 2018;41:1024-1033. PMID 29962399
  9. Lazzaroni E, Ben Nasr M, Loretelli C et al. Anti-diabetic drugs and weight loss in patients with type 2 diabetes. Pharmacol Res. 2021;171:105782. PMID 34302978

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