Glucose Metabolism “Derangements” from Second Generation Antipsychotics Clarified


New Zealand and Chinese investigators believe they have clarified the mechanisms by which second generation antipsychotics cause serious “derangements” in glucose metabolism in the human body. Reporting in Schizophrenia Research, the researchers write that previously many have assumed that these negative metabolic effects were due to increases in insulin resistance, but during more precise animal studies using clozapine they found otherwise.

“Taken together these results suggest that clozapine does not have any direct effect on glucose metabolism in the liver but it simultaneously stimulates insulin and glucagon secretion, a situation that would allow for the concurrent presence of high glucose and high insulin levels in treated animals,” conclude the researchers.

Clozapine directly increases insulin and glucagon secretion from islets: Implications for impairment of glucose tolerance (Smith, G.C. et al. Schizophrenia Research. August 2014. DOI:


  1. “We also show that the non-peptidic glucagon receptor like peptide-1 (GLP-1) receptor agonist Boc5 was able to overcome the inhibitory effects of clozapine on glucose metabolism.”

    Maybe we’ll get novel drugs for treating atypical neuroleptic caused obesity. Yippee.

    Report comment

    • I’m afraid you’re right… :/. Btw, I’ve also seen people looking at the correlation between obesity, diabetes and “serious mental illness” concluding that there has to be underlying genetic risk factor for all of them. I happen to be a scientist in training and when I see things like that I can’t help a facepalm.

      Report comment

  2. A continued saga of Boc5, the first non-peptidic glucagon-like peptide-1 receptor agonist with in vivo activities.
    He M1, Guan N, Gao WW, Liu Q, Wu XY, Ma DW, Zhong DF, Ge GB, Li C, Chen XY, Yang L, Liao JY, Wang MW.
    Author information

    Glucagon-like peptide-1 (GLP-1)-based therapy presents a promising option for treating type 2 diabetes. However, there are several limitations relative to the peptidic GLP-1 mimetics currently on the market or under development. This concern has led to a continued interest in the search for non-peptidic agonists for GLP-1 receptor (GLP-1R). Here, we briefly review the discovery, characterization and current status of a novel class of cyclobutane-derivative-based non-peptidic agonists for GLP-1R, including Boc5 and its newly discovered analogue WB4-24. Although the oral bioavailability of such compounds still poses great challenges, the progress made so far encourages us to identify a truly ‘druggable’ small molecule agonist for GLP-1R.

    Report comment

  3. All I know is that during the months of Zyprexa withdrawal hell that extra hunger it caused rebounded in the other direction into nausea and a total lack of appetite. Nothing like knowing your starving and at the same time being repulsed at the idea of eating.

    Report comment

  4. I guess this is a very technical way of explaining how those conned or forced into taking toxic neuroleptic drugs get diabetes, obesity, metabolic syndrome that then contribute to heart attacks, stroke along with the brain damage and other lethal effects that cause early death by about 25 years on average.

    Can’t wait for a technical article on how boys develop breasts from some of these toxic drugs!

    Report comment